United States
Environmental Protection
Agency
Office of
Pesticides and Toxic Substances
Washington DC 20460
December 1984
Pesticides
«*EPA
Alachlor
Special Review Position
Document 1
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ALACHLOR
POSITION DOCUMENT 1
OFFICE OF PESTICIDE PROGRAMS
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
DECEMBER 31, 1984
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EXECUTIVE SUMMARY
This Position Document (PD) 1 presents the basis for the
initiation of a Special Review of all pesticide products con-
taining the active ingredient, alachlor. Laboratory studies
in rats and mice have demonstrated the potential for alachlor
to produce tumors in mammals. The Agency has determined
that the weight of evidence demonstrates that alachlor is
oncogenic to laboratory animals and, in the absence of data on
humans, it is prudent to treat alachlor as a probable human
carcinogen. Further, certain uses of alachlor are associated
with significant exposures, therefore, the Agency has
determined that certain uses of alachlor may result in
unreasonable adverse effects to man.
The major pesticidal uses of alachlor are the preemergent
application to field corn, soybeans and peanuts, which comprise
about 99% of the chemical's use. The remaining uses, also
involving preemergent application, are on sweet corn, popcorn,
cotton, dry beans, grain sorghum, green peas, lima beans (green),
sunflowers and ornamentals.
The Agency has determined that use of products containing
alachlor poses a risk to human health through significant
exposure to a substantial number of workers involved in applica-
tion of pesticides. Moreover, the general public is exposed
to alachlor in the diet from residues in treated crops and in
drinking water in certain areas.
A preliminary analysis of the benefits associated with
each registered use demonstrates that viable, effective alter-
natives are available and in use.
The following regulatory options will be considered by the
Agency in reaching the proposed regulatory decision:
(1) Continuation of registration without changes.
(2) Continuation of registration with modification to
terms and conditions of registration.
(3) Cancellation of registration.
Certain labeling restrictions have been required in the
alachlor Registration Standard in order to address the risks
from alachlor use during the period necessary to complete the
administrative process initiated by this Position Document
(See Chapter I.B.2). These measures are intended to address
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risks to applicators and the general public during and after
use of the pesticide:
(1) Use of protective clothing;
(2) Tumor hazard warning statement;
(3) Water contamination warning statement;
(4) Prohibition of aerial application;
(5) Prohibition of use on potatoes; and
(6) Handling instructions to reduce applicator exposure.
A special information and training program available to
all applicators is being required in the alachlor
Registration Standard. Alsor data to more fully assess ground
water contamination and runoff contamination of surface water
are being required on an accelerated schedule.
It is emphasized that this Special Review, which presumes
against registration and continued registration of alachlor under
the present terms and conditions, is not a notice of intent to
cancel the registration of the pesticide, and may or may not
lead to cancellation.
This Position Document invites all registrants, applicants
and interested parties to comment and submit evidence in rebuttal
of the presumptions listed in Chapter II of this document.
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Table of Contents
Executive Summary Page
I. Introduction
A. General Background and Organization 1
B. Legal Background
1. The Statute 1
2. The Registration Standard Process 2
3 . The Special Review Process 3
C. Regulatory History of Alachlor
1. Uses and Reg istrat ion 3
2. Tolerances 4
3. Registration Standard and Special Review 6
II. Risk Assessment 7
A. Hazard Identification (Qualitative Risk Assessment)
1. Physical-Chemical Properties
and Exposure Pathways 7
2. Structure-Activity Relationships 8
3. Metabolic and Pharmacokinetic Properties 9
4. Non-Oncogenic Toxicological Effects 9
5 . Short Term Tests 10
6. Oncogenicity H
7 . Human Stud ies 14
8 . Weight-of-the-Evidence 15
B . Dose-Response Assessment 16
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Page
C. Exposure Assessment .................................. 19
1. Dietary Exposures
a. Residues from Treated Raw Agricultural
Conunod ities ................................... 19
b. Exposure Through Drinking Water ............... 23
I. Exposure Through Drinking Water from
Ground Water Sources ...................... 24
II. Exposure Through Drinking Water from
Surface Water Sources
A. Monitoring Data ....................... 30
<
B. Modeling Assessment ................... 37
2 . Appl icator Exposure .............................. 44
D. Risk Characterization ................................ 51
1. Dietary Risks
a. Risks from Consumption of Raw
Agricultural Commodities .................... 51
b . Drinking Water Risks ........................ 55
2 . Appl icator Risks ................................. 56
3. Uncertainties in the Risk
Assessment ...................................... 60
E. Toxicity of Alternatives to Alachlor ................ 61
F. Proposed Risk Reduction Measures .................... 65
III. Benefits Summary
A. Introduction ........................................ 69
B. Field Corn .......................................... 71
C . Peanuts . . ........................................... 72
D. Soybeans ............................................ 72
E . Sweet Corn and Popcorn .............................. 73
F. Cotton, Dry Beans, Grain Sorghum, Green Peas,
Green Lima Beans, Sunflowers and Ornamentals ........ 73
ii
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Page
G. Cabbage - Emergency Action 73
IV. Additional Grounds for Review 76
A. Risk/Benefit Information 76
B. Rebuttal Submission Procedures 79
C. Duty to Submit Information on Adverse Effects 79
D. Public Comment Opportunity 80
REFERENCES
111
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I. Introduction
A. General Background and Organization
The Federal Insecticide, Fungicide and Rodenticide Act, as
amended (FIFRA) [7 U.S.C. 136 et seq. ] , requires the Environmental
Protection Agency (EPA) to review the risks and benefits of the
uses of pesticides suspected of causing unreasonable adverse
effects to human health or the environment.
In November, 1984, EPA issued another document, "Guidance
for the Registration of Pesticide Products Containing Alachlor
as an Active Ingredient" (Registration Standard). As part of
developing that assessment, the Agency stated its determination
that alachlor (2-chloro-2',6'-diethyl-N-(methoxymethyl)-
acetanilide, CAS number 15972-60-8, meets one of the risk criteria
used to determine whether it causes unreasonable adverse effects
[40 CFR 162.11(a)(3)(ii)(A)]. In response to that determination,
a Special Review is being initiated on alachlor. This review
was prompted by studies showing that alachlor caused oncogenic
effects in test animals. This Position Document (PD 1) reviews
the Agency's assessment of the risks and benefits of the uses
of alachlor, particularly the uses on peanuts, field corn and
soybeans, and requests registrants and other interested persons
to submit rebuttals and other information on the presumption
and to submit any other data on the risks and benefits of
alachlor .
This document contains four chapters. This introductory
section, Chapter I, provides background information on alachlor
and the pesticide regulatory process through which the chemical
will pass, resulting in an Agency regulatory decision. Chapter
II evaluates the potential human health risks of alachlor,
and briefly describes the laboratory evidence of toxicity,
available exposure data and the Agency's assessment of risk.
Part III summarizes the economic benefits of alachlor and the
assumptions and limits of the assessment of benefits. Chapter
IV solicits additional information with respect to possible
adverse effects from exposure to alachlor and describes the
procedures by which interested parties may submit such
information.
B. Legal Background
1. The Statute
The Federal Insecticide, Fungicide and Rodenticide Act,
as amended (FIFRA) [7 U.S.C. 136 et seq.] requires the
Environmental Protection Agency (EPA) to regulate all pesticide
products through review of the risks and benefits of the uses
of these products. The Administrator must determine that
the use of a pesticide will not result in "unreasonable adverse
effects on the environment," defined in Section 2(bb) of FIFRA
as "any unreasonable risk to man or the environment, taking
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into account the economic, social and environmental costs and
benefits of the use of any pesticide." In other words, any
decision on pesticide registration must take into account both
risks and benefits from the pesticide's use.
Section 6(b) of FIFRA authorizes the Administrator to
issue a notice of intent to cancel the registration of a pesticide
or to change its classification if it appears that the pesticide
or its" labeling "does not comply with the provisions of [FIFRA]
or, when used in accordance with widespread and commonly recognized
practice, generally causes unreasonable adverse effects on the
environment".
The Administrator may also cancel the registration of a
pesticide if its labeling does not comply with the misbranding
provisions of FIFRA which require the labeling to contain lan-
guage "adequate to protect health and the environment" [FIFRA
Section 2(q)].
2. The Registration Standard Process
Under FIFRA Section 3(g), Congress has directed EPA to
determine whether it can re-register all previously registered
products so as to bring their registrations and their data
bases into compliance with current requirements. To effect
this, the Agency has developed new review procedures. Under
those procedures, EPA publishes documents called "Registration
Standards," each of which discusses a particular pesticide
active ingredient. Each Registration Standard summarizes all
the data (in its files) used in the Agency's development of a
comprehensive regulatory position on the conditions and require-
ments for registration of all existing and future products which
contain the active ingredient. These conditions and requirements,
which must be met to obtain or retain full registration or
reregistration under Section 3(c)(5) of FIFRA, include the
submission of needed scientific data which the Agency does not
now have, compliance with standards of toxicity, composition,
labeling, packaging and satisfaction of the data compensation
provisions of FIFRA Section 3(c)(l)(D).
The Registration Standard review process also includes a
comparison of information about potential adverse effects of
the specific uses of the pesticide with risk criteria listed
in 40 CFR 162.11(c), and thereby assists in determining whether
a product should be a candidate for the Special Review Process.
3. The Special Review Process
The Special Review Process provides a mechanism through
which the Agency gathers risk and benefit information about
pesticides which appear to pose risks of adverse effects to
human health or the environment which may be unreasonable.
Through issuance of various position documents (PDs), the
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Agency invites pesticide registrants, USDA, FDA, user groups
environmental groups and other interested persons to partici]
in the Agency's review of suspect pesticides.
The Special Review regulations in 40 CFR 162.11(c)(5)
prescribe regulatory criteria for the Agency's preliminary
assessment of a pesticide's health and environmental effects
and provide that a Rebuttable Presumption Against Registration
(RPAR or Special Review) shall arise if the Agency determines
that any of the risk criteria have been met.
Benefits evidence, submitted to and/or gathered by the
Agency, must be evaluated and considered in light of the risk
information. If the Agency determines that the risks appear
to outweigh the benefits, the Agency can initiate action under
FIFRA Section 6(b)(l) to cancel the registration for all or for
specific uses, or to cancel the registration unless the terms
and conditions of the registration or use are modified to
adeguately reduce the risks of continued use. FIFRA Section
6(b)(2) proceedings are appropriate where a pesticide use
appears to pose unreasonable adverse effects, and the Agency
seeks to obtain additional information on risk or benefits
during an administrative hearing in order to make a decision
on the ultimate fate of the pesticide's uses.
C. Regulatory History of Alachlor
1. Uses and Registration
Alachlor is produced in the United States by Monsanto
Chemical Co. It has been registered since 1969 as a selective
herbicide for control of many preemergent broadleaf weeds and
grasses. Registered uses include selective weed control in
cultivated agricultural land and woody ornamentals.
Alachlor is registered for use against a number of weed
and grass species. Among the target species are barnyardgrass,
crabgrass, foxtails, goosegrass, signalgrass, witchgrass,
fall and Texas panicum, nightshade, carpetweed, pigweed,
purslane and sandbur.
Alachlor is usually applied as a broadcast surface treat-
ment by ground or air eguipment using 15 or more gallons of
water per acre. It may also be applied as a band treatment.
The most commonly used formulations are the 43.5 and 45.1%
emulsifiable concentrates (EC) and the 10 and 15% granular (G)
products. A microencapsulated (ME) formulation was registered
in 1983 for use on dry beans, lima beans, peas, potatoes, and
soybeans. The alachlor EC formulations are generally applied
as tank mixes with other herbicides. Alachlor also is sold in
formulations mixed with either atrazine or glyphosate. Appli-
cation rates vary from 1.5 to 8 pounds active ingredient per
acre depending upon target species and use site.
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According to EPA records, Monsanto is the only company
holding Federal registrations for nine alachlor products. There
are also nine intrastate registrations for alachlor which are
marketed pursuant to 40 CFR 162.17.
2. Tolerances
Tolerances were established in 40 CFR 180.249 for alachlor
and its metabolites (calculated as alachlor) resulting from
the use of the herbicide in or on raw agricultural commodities.
Tolerances are maximum permissible residue levels established
pursuant to the Federal Food, Drug and Cosmetic Act. These
tolerances are presented in Table 1.
There are also several pending petitions for alachlor
tolerances in which additional tolerances have been requested
for sugarcane at .2 parts per million (ppm), sugarcane forage
and fodder at .2 ppm, cabbage at .3 ppm, sweet corn at .2 ppm,
sweet corn forage and fodder at .5 ppm, and soybean hay at 1.0
ppm. Petitions are also pending which request an increase in
the peanut tolerance from 0.05 ppm to .1 ppm and an increase
in the potato tolerance from 0.1 ppm to 1.0 ppm. During the
Special Review, the Agency will not be inclined to grant these
pending tolerance petitions.
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Table 1. Alachlor Tolerances
Commodity
Beans, dry
Beans, forage
Beans, lima (green)
Cattle, fat
Cattle, meat-by-
products
Cattle, meat
Corn, fodder
Corn, forage
Corn, fresh, including
kernels and corn with
husks removed
Corn, grain
Cotton, forage
Cottonseed
Eggs
Goats, fat
Goats, meat-by-
products
Goats, meat
Hogs, fat
Hogs, meat-by-
products
Hogs, meat
Horses, fat
Horses, meat
Milk
Peanuts
Peanuts, forage
Peanut, hay
Peanut, hulls
Peas, forage
Peas, hay
Peas, pods removed
Potatoes
Poultry, fat
Poultry, meat-by-
products
Poultry, meat
Sheep, fat
Sheep, meat-by-products
Sheep, meat
Sorghum, fodder
Sorghum, forage
Sorghum, grain (milo)
Soybeans
Soybean, forage
Soybean, hay
Sunflower seed
Tolerance
0 . 1 ppm
0 . 2 ppm
0 . 1 ppm
0.02 ppm
ii
ii
0 . 2 ppm
n
0.05 ppm
0 . 2 ppm
ii
0.05 ppm
0.02 ppm
n
it
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n
n
n
n
n
n
0.05 ppm
3 . 0 ppm
H
1 . 5 ppm
0 . 2 ppm
n
0 . 1 ppm
n
0.02 ppm
II
II
0.02 ppm
H
n
1 . 0 ppm
n
0 . 1 ppm
0 . 2 ppm
0.75 ppm
0 . 2 ppm
0.25 ppm
Citation
(40 CFR 1
Alachlor
and Form
80.249
and its
metabolites calcu-
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alachlor)
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3. Registration Standard and Special Review
The preparation of the Registration Standard for alachlor
was initiated in 1982. The Registration Standard for alachlor
has been developed and was published in November, 1984. During
the analysis, the Agency reviewed information about the potential
adverse effects, most specifically oncogenicity, associated
with uses of alachlor that met the risk criterion listed in 40
CFR 162.11 (c). Based on that information the Special Review
is being initiated for the pesticide.
Certain labeling restrictions are being required in the
alachlor Registration Standard in order to address the risks
from alachlor use during the period necessary to complete the
Special Review process. The labeling restrictions include:
(1) Use of protective clothing;
(2) Tumor hazard warning statement;
(3) Water contamination warning statement;
(4) Prohibition of aerial application;
(5) Prohibition of use on potatoes; and
(6) Handling instructions to reduce applicator exposure.
These measures are intended to address risks to applicators and
the general public during and after use of the pesticide. These
labeling restrictions are discussed further in Chapter II.E.
The Agency is requiring additional data on an accelerated
basis on the leaching and mobility of alachlor to examine the
potential of alachlor to contaminate ground water. In addition,
a monitoring study to evaluate the manner and extent of
contamination of ground and surface water is being required.
A special information and training program available to
all users of alachlor is also being required in the Registration
Standard.
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II. Risk Assessment
In reviewing the available data on alachlor during the
Registration Standard process, the Agency determined that the
risk criterion for oncogenicity (40 CFR 162.11(C)(5) ) was met.
This section consists of the oncogenicity risk assessment,
incorporating many of the procedures and principles espoused
by the Agency (NAS, 1983; OSTP, 1984; EPA, 1984).
The risk assessment process consists of four steps. In
the first step, Hazard Identification, all relevant information
is presented and a qualitative weight-of-the-evidence judgment
is reached on the likelihood that the pesticide is a human
carcinogen. In the second step, Dose-Response Assessment,
experimental data are used in conjunction with certain assump-
tions and a mathematical model to extrapolate the likely upper
bound of human cancer risk to the low dose range. The third
step is Exposure Assessment in which human exposures via various
routes and sources are estimated. Finally, in the fourth
step, Risk Characterization, the results of the Exposure and
Dose-Response Assessments are coupled to project the plausible
upper bound of the cancer risk under different conditions of
exposures. This step also includes a summary of the strength
of the qualitative evidence, plus a treatment of the uncertainties
in the final assessment.
A. Hazard Identification (Qualitative Risk Assessment)
1. Physical-Chemical Properties and
Exposure Pathways
Alachlor is the common name for 2-chloro-2',6'-diethyl-
N-(methoxymethyl)acetanilide, CAS number 15972-60-8, a pre-
emergent herbicide. Other names for this pesticide include
2-chloro-N-(2,6-diethylphenyl)-N-(methoxymethyl)acetamide,
CP 50144 and Lasso.
Alachlor has an empirical formula of Ci4H2oNC>2Cl, a
molecular weight of 269.77. Table 2 lists chemical and physical
properties of alachlor.
Alachlor is registered for use as a pre-emergence herbicide
on corn, soybeans and other crops. Corn and soybeans account
for 98% of total alachlor usage. This use pattern and the
environmental behavior of alachlor suggest that the principle
pathways of human exposure are by direct contact during applica-
tion and ingestion of foodstuffs and drinking water which contain
alachlor residues.
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Table 2. Physical and Chemical Properties of Alachlorl
Melting Point
Specific Gravity
Solubility
Octanol/Water Partition
Coefficient
Stability
Appearance at room temp. —
40-41°C
1.133(25/15.6°C)
Soluble in ether, acetone,
benzene, alcohoHunspecified)
and ethyl acetate; slightly
soluble in hexane; solubility
in water - 240 ppm
434
Stable (first detectable
heat evolution at 105°C)
White, crystalline solid
at 23°C.
iMonsanto, 1973, 1979.
2. Structure-Activity Relationships
Alachlor is a substituted acetanilide. The Agency has
concluded that at least one other chemical in this class is
oncogenic in laboratory animals. Metolachlor (2-chloro-2'-ethyl-6'
-methylphenyl-N(2-methoxy-l-methylethyl) acetanilide) has
produced tumors in the rat liver (Ciba-Geigy, 1979). Other
structurally-related chemicals have either not been adequately
tested or the review of testing has not yet been completed by
the Agency.
\
CH2CH3
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CH2OCH3
CCH2C1
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c —
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CHCH2OCH3
CCH2C1
H
o
ALACHLOR
METOLACHLOR
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3. Metabolic and Pharmacokinetic Properties
A gavage metabolism study in the rat (Monsanto, 1983a)
indicated that alachlor is rapidly metabolized and eliminated
as conjugates-of mercapturic acid, glucuronic acid and sulfate
in urine and feces (37.6 to 45.0% in urine and 47.7 to 51.1% in
feces of males: 42.5 to 53.2% in urine and 37.0 to 49.3% in
feces of females). Appproximately 89% of the dosages were
eliminated during the 10-day study, with most of the elimination
occurring within the first 48 hours (half life of .2 to 10.6
hours), followed by a slower phase (half life of 5 to 16 days).
Elimination as CC>2 was minimal.
Radioactivity from the administered dose was found in the
blood and in the spleen, liver, kidney and heart which may be
a reflection of the amount of blood in those organs. In addition,
a relatively high level of radioactivity was also found in the
eyes, brain, stomach and ovaries. These data assume added
significance in light of the treatment-related lesions observed
in the 2-year rodent feeding studies discussed below.
A dermal absorption study (Monsanto, 1981a) in Rhesus monkeys
indicated that approximately 50% of dermally applied alachlor
EC formulation was absorbed within 24 hours. Additional jLn
vitro dermal absorption studies were performed with human skin
which suggest that the dermal absorption of the microencapsulated
product may be approximately 12% (Monsanto, 1981b). However,
due to difficulties associated with these studies, e.g. low
recovery of the test material and metabolites, the usefulness
of these data are limited. Additional data on dermal absorption
are being required through the Registration Standard. No
information is available on absorption by the inhalation route
of exposure, but, as noted below, inhalation exposure of appli-
cators appears to be insignificant compared to dermal exposure.
4. Non-Oncogenic Toxicological Effects
Alachlor exhibits relatively low acute toxicity by the oral
(rat LD5n=.93 g/kg), dermal (rabbit LD5Q=13.3 g/kg), or inhal-
ation (rabbit LC5Q>5.1 ml/1) routes of exposure (Monsanto,
1978a and 1981c). Although technical alachlor is a skin sensitizer
and causes ocular lesions upon chronic exposure, the technical
product has only slight skin and eye irritation potential
after an acute exposure (Monsanto, 1978b and 1984a).
A two year rat feeding study in the Long-Evans strain showed
alachlor to be toxic at all doses tested (14.0, 42.0 and 126.0
mg/kg/day) (Monsanto, 1982). The principal toxic effects
observed were hepatotoxicity and an ocular lesion, referred to
as the uveal degeneration syndrome (UDS). UDS is characterized
in its mildest form by free floating iridial and choroidal
pigment in the ocular chamber and pigment deposition on the
cornea and lens. In its most severe form, the syndrome is
characterized by bilateral degeneration of the iris and diminution
of the size of the ocular globe with secondary total cataract
formation.
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A follow-up two-year feeding study in the same strain of
rat was conducted at 0.5, 2.5 and 15.0 mg/kg/day (Stout, 1983a) .
There was a small increase at the high dose of animals exhibiting
the initial stage of UDS, specifically molting of retinal pig-
mentation. The 2.5 mg/kg/day was judged to be the NOEL for UDS.
The Agency has subsequently received a study in Long-Evans
rats run concurrently with the previously discussed study
utilizing a higher dose of alachlor, 126 mg/kg/day, administered
for less than a lifetime (Stout, 1983b). This study indicated
that UDS, once established, is an irreversible condition. UDS
has not been observed in the other toxicology studies that have
been conducted to date.
In a six-month dog feeding study, alachlor was tested at
5.0, 25.0, 50.0 and 75.0 mg/kg/day and showed dose related
hepatotoxicity at all doses (Ahmed, 1981). Increased absolute
and relative liver weights were observed at all dose levels for
males and at dose levels of 25 mg/kg/day and above for females.
Liver fatty degeneration and biliary hyperplasia occurred in
both sexes at dose levels of 25 mg/kg/day and greater.
In a three generation rat reproduction study, alachlor
was tested at 3.0, 10.0 and 30.0 mg/kg/day and showed a repro-
duction NOEL at 10.0 mg/kg/day and reproduction lowest-observed-
effect-level at 30.0 mg/kg/day, with indications of renal
toxicity observed in F2 adult males and F3 pups (Schroeder,
1981). The renal toxicity consisted of kidney discoloration,
chronic nephritis and increased relative and absolute kidney
weights.
In a teratology study in the rat (Rodwell, 1980), alachlor
was administered by gavage at dose levels of 50, 150 and 400
mg/kg/day. A maternal and fetotoxic NOEL was established
at 150 mg/kg/day in this study with no teratogenic potential
indicated at the highest dose tested, 400 mg/kg/day.
An additional rabbit teratology study was recently submitted
but was considered inadequate to assess the teratogenic potential
of alachlor due to the use of an inappropriate vehicle, only
minimal evidence of maternal toxicity, a high incidence of pre-
implantation loss in the high dose, inadequate historical data,
lack of individual fetal data for body weights and variations
as well as other problems (Schardein, 1983).
5. Short Term Tests
The available mutagenicity testing data on alachlor are
limited. A rec-assay was conducted at 6 concentrations (20 to
20,000 ug/plate) in B. subtilis strains M45 and H17 and showed
no evidence of test compound-induced inhibition. The reverse
mutation assay conducted at 6 concentrations (10 to 15,000
ug/plate) in E. coli strain WP2 her and S. typhimurium strains
TA1538, TA1537, TA1535, TA98 and TA100, with and without S9
metabolic activation, was also negative (Shirasu, 1980).
10
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A recently submitted in vitro/in vivo hepatocyte DNA repair
study in rats indicated that alachlor is weakly genotoxic at
1000 mg/kg in the Fischer 344 strain of rat (Mirsalis, 1984).
A recently submitted in vivo bone marrow cytogenetics study
(Farrow, 1984) was determined to be negative for mutagenic
potential but is considered to be scientifically unacceptable
due to the lack of demonstration of the appropriateness of
the dose levels used. As outlined in the Registration Standard,
additional genotoxicity testing information is being required.
6. Oncogenicity
Alachlor feeding studies have demonstrated oncogenic effects
which include lung tumors in mice and stomach, thyroid, and
nasal turbinate tumors in rats. The results of these studies
are described below.
Female mice of the CD-I strain fed technical grade alachlor
in the diet for 18 months at dosage rates of 26, 78 and 260
mg/kg/day developed a statistically significant increase (p<0.05)
in lung bronchioalveolar tumors at the highest dose tested
(Daly, 1981a). The increase of lung tumors in male mice was
not significant. Numerical increases were observed in the
incidence of liver and uterine tumors in the high dose group
but these increases were not statistically significant. The
technical material in this study was stabilized with epichloro-
hydrin (0.5%) for the first eleven months and with another
intentionally added inert for the remainder of the study.
This change in material tested came about because the registrant
removed epichlorohydrin from technical alachlor, replacing it
with a different stabilizer.
Two chronic feeding studies were conducted in the Long Evans
strain of rat with alachlor. In the first study, the technical
material was stabilized with epichlorohydrin during the first
year of the study (Daly, 1981b) and fed to 50 animals/sex at
dose levels of 14, 42, and 126 mg/kg/day. During the second
year of this study, alachlor stabilized with another intentionally
added inert was the test material.
Dose-related responses were observed for tumors of the
nasal turbinate of both sexes for the mid and high doses. Also,
statistically significant increases were observed in the incidence
of malignant stomach tumors (described by the authors as neoplasms
pluripotent in ability to form a mixed carcinomasarccma-type
tumor) in the high dose of both sexes (p<0.001). In addition,
thyroid follicular tumors (adenomas plus carcincmas) appeared
to increase in both sexes at the high-dosage level with the
increase being significant (p<0.001) in males. The incidences
of the nasal turbinate, stomach and thyroid tumors as well as
other tumors, i.e. liver and brain, considered of potential
biological significance is shown in Table 3. Table 3 also
presents the histological diagnoses of the tumors of interest.
11
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Table 3. Tumor Incidence in Rats
Dosage (Stout
mg/kg/day
No. of tissues examined
and incidence of animals
with tumors
Nasal turbinate tumors
"Adenoma
°Adenocarcincma
Stomach
"Malignant tumors
-Mixed carcincmasarcoma
-Ondifferentiated
sarcoma
-Undi f f erent iated
-Adenocarc inoma
-Le iomyosarcoma
-Anaplastic sarcona
-Osteosarcoma
Thyroid
°C-cell adenoma
carcinona
"Follicular adenoma
carcinoma
Brain
0 Neuroep i the 1 i oma
"Ependymoma
Liver
"Hepatoma
"Nodular hyperplasia
"Carcinoma
M
61
42
7
68
3
2
-
—
-
1
—
70
4
0
8
10
70
1
0
70
3
0
2
1983b)#ML-80-224
126
GI*
F
25
11
2
31
19
6
5
i
3
3
1
—
31
3
0
4
0
31
1
0
31
1
1
2
GUI*
M F
17 46
10 19
0 1
20 49
0 1
- 1
20 49
1 2
0 1
1 3
1 1
20 49
0 1
0 0
20 49
0 0
0 1
0 1
(Stout 1983a) #ML-80-186 (Daly 1981b) #BD-77-421
0 .5 2.5 15 0 14 42 126
M'FMF. MFMFMFMFMFMF
44 42 47 42 44 47 45 48 46 49 46 47 41 45 42 48
0 0 0 0 0 1 15 14 0 0 0 0 10 4 23 10
0000000000001100
50 50 50 50 50 50 49 48 49 50 50 50 50 50 50 50
00001000000001 17 23
11 17
-__-!__________
4
49 49 50 49 49 49 49 47 48 49 50 44 49 46 50 49
5232746342532473
0000100010100100
21413042100012 11 2
1301112100000022
50 50 50 50 50 50 49 49 50 50 50 50 50 50 50 50
0000000000000000
0000000000000221
50 50 50 50 50 50 50 49 50 50 50 50 50 50 50 50
1001000010002113
0 0 0 0 00 0 1 0 2 0 1 1 2.4:: 1
20112002000000 ;0 0
*GI: animals maintained on treated diets for 2-year; GUI: animals maintained on treated diets for only 5 to
6 months.
12
-------
In the second two-year feeding study (Stout, 1983a)f
throughout which an inert different from epichlorohydrin
was used as a stabilizer in the test material, three treatment
groups of 50 male and 50 female Long-Evans rats received 0.5,
2.5, and 15 mg/kg/day. Data from an additional study which ran
concurrently with the previously discussed study have recently
been submitted (Stout, 1983b). This additional study (Stout,
1983b) used a fourth treatment group, 126 mg/kg/day, that was
exposed to the new technical material (with the new stabilizer
in place of epichlorohydrin). The design of this study was
different from the previous study (Stout, 1983b) because it
used a variety of dosing regimens and had the primary purpose
of investigating the nature and reversibly of the ocular lesions
(UDS). The animals in this additional dose level were subdivided
into three groups. One group was sacrificed and examined
after approximately 8 months of treatment, one was treated for
five to five and one half months and then put on control diet
for the remainder of the two year period and the third group
was treated for the entire two year period. The second group
was selected from among the larger group primarily on the
basis of appearance of early ocular effects rather than random
assignment. The biased selection process inherent in the
design of this study limits its usefulness for the quantitative
assessment of oncogenic potential. However, the results are
useful in qualitative assessment of the weight-of-the-evidence
for the oncogenicity of the new technical product not stabilized
with epichlorohydrin. This study indicates that the tumor
response observed in the earlier study (Daly, 1981b) cannot be
explained by the presence of epichlorohydrin in the test material
and suggests that partial lifetime exposure (approximately
one-fourth of the lifespan of the animals) can result in a
similar tumor incidence as a lifetime exposure.
The nasal epithelial adenoma response was statistically
significant in both sexes of both chronic rat studies (p<0.001).
The incidence of this neoplasm in the second chronic rat study
is presented in Table 3. In addition to the tumors presented
in the table, it should be noted that there was a submucosal
gland adenocarcinoma observed in a mid-dose male in the second
study (Stout, 1983a) . For risk assessment purposes, this
submucosal gland adenocarcinoma was not combined with the
adenomas and adenocarcinomas of the nasal turbinate because it
was sufficiently different from other nasal tumors observed to
be considered as not treatment related.
An increase was also noted in the incidence of thyroid
follicular cell adenomas or carcinomas in males in the second
study, with 4, 4, 6, and 18 (8%, 8%, 12%, and 25%) of the males
in the 0.5, 2.5, 15.0 and 126 mg/kg dose groups respectively
having this finding compared to 3 (6%) in the control group.
A rare stomach tumor (an undifferentiated sarcoma) was found
in a 2.5 mg/kg male and it is considered biologically significant
13
-------
in view of its occurrence in several animals at the 126 mg/kg
dose level in the second study. No stomach tumors were observed
in control animals in any of these chronic rat studies. Several
primary brain tumors were noted in treated animals in both the
earlier chronic rat study and in the 126 mg/kg dose level
extension of the more recent study. The brain tumors observed
in the first study were classified as ependymomas, whereas
several neuroepitheliomas were observed in the second study.
The increased incidences were not significant compared to the
control groups. However, the registrant has concluded that
these tumors "were possibly due to, or secondary to, treatment
with the compound", apparently due to the rarity of this tumor
in Long-Evans rats. Although the incidence of ependymoma does
not appear to be compound-related, the Agency has not yet
concluded whether the incidence of neuroepithelioma is biologi-
cally significant and has requested historical control data
from the registrant regarding the incidence of this tumor type.
Epichlorohydrin (ECH), when tested alone, has been shown
to induce both nasal turbinate tumors and stomach tumors in
rats (Laskin, 1980; Konishi, 1980). These ECH-associated nasal
turbinate tumors appear to be of similar histogenic origin as
the ones noted in the alachlor rat studies. The ECH-associated
stomach tumors were not malignant, in contrast to those observed
in the studies with alachlor. It is difficult to estimate the
contribution, if any, ECH made to the results observed in the
rat and mouse studies due to the following:
o The rats were of different strains in the alachlor and
ECH studies.
o ECH was administered through different routes of
exposure (i.e. inhalation exposure (Laskin, 1980); oral
exposure through treated water (Konishi, 1980); and
oral exposure through treated feed (Daly, 1981b).
o ECH was administered to the animals for different
durations.
However, the occurrence of these same tumor types in the
second rat study in which a different stabilizer replaced ECH
(and its 126 mg/kg/day dose extension), demonstrates an alachlor
related effect, independent of ECH.
7. Human Studies
v The Agency is unaware of any human studies that have inves-
tigated the oncogenicity of alachlor. There is one limited
epidemiological study which investigated the ocular status of
workers in a plant where alachlor was manufactured (Coleman,
1980) but no attempt was made to address oncogenic effects in
this study.
14
-------
8. Weight-of-the-Evidence
The goal of the Hazard Identification step of the Cancer
Risk Assessment is to reach a qualitative judgment on the
evidence that alachlor may be a human carcinogen.
The data in Table 4 show that alachlor has demonstrated
statistically and biologically significant oncogenic responses
at multiple sites at multiple doses in two sexes of one rodent
species and at one site at one dose in one sex of a second
species. Several oncogenic observations were replicated in
the rat (see Table 3).
Table 4. Summary of Statistically Significant Oncogenic
Responses in Alachlor Feeding Studies in Mice
and Rats.
Mouse Rat
Lung—at one dose (F) Nasal turbinates--at three doses (MF)1
Stomach—at one dose (MF)-'-
Thyroid—at one dose (M)l
Thyroid—at one dose (F)
I/— Seen in more than one study.
All observed stomach tumors were malignant as were
several of the tumors observed at other sites. In addition,
the incidence of nasal turbinate tumors observed after two
years in rats exposed for 5 to 6 months demonstrates that less
than lifetime exposure is sufficient to elicit an oncogenic
response in rats (Stout, 1983b).
As further supporting evidence, it can be noted that
alachlor is structurally similar to another substituted acet-
anilide (metolachlor) which has demonstrated oncogenic effects
(neoplastic nodules of the liver (NAS, 1980)) in the Sprague-
Dawley strain of rat. Mutagenicity tests of alachlor have
produced negative results (with the possible exception of the
recently submitted DNA hepatocyte repair study which indicated
DNA repair activity at the highest dose tested), but the Agency
is requesting additional genotoxicity data derived from a
broader range of test systems.
The Agency concludes that alachlor is a demonstrated
animal oncogen. There are no data available concerning direct
evidence of oncogenic effects in humans. Therefore, the Agency
takes the position that alachlor should be viewed as having
the potential to be a human oncogen. In the context of the
15
-------
categorization adopted by EPA modification of the IARC classi-
fication scheme (EPA, 1984), alachlor would be assigned to
category B2, a probable human carcinogen.
B. Dose-Response Assessment
The upper bound estimates of excess cancer risk presented
in this document are based on extrapolation from tumor rates
in both males and females in the second rat oncogenicity study
without the high dose (i.e. using doses 0, 0.5, 2.5, and 15 mg/kg
(Stout, 1983a)). The reasons for this choice and the effect of
including other available data sets are discussed below. Extra-
polation is done using the linearized multistage model (computed
by the Global 83 computer program). This is in keeping with
Agency policy for those chemicals for which information regarding
the mechanism of oncogenicity is unknown. Also in keeping with
Agency policy, the interspecies extrapolation for oncogenic
effects is accounted for by expressing the dose in terms of
weight of alachlor per body surface area per day, rather than
weight per body weight per day (EPA, 1984). The effect of
treating interspecies differences this way is to increase the
experimental rat estimate of risk approximately five fold in
humans.
The mouse oncogenicity study is not being used for
quantitative risk assessment purposes because the tumor types
observed in the chronic rat studies (nasal turbinate, stomach
and thyroid) are considered to be more reliable predictors of
oncogenic potential than the mouse lung tumor (IARC, 1983).
Furthermore, the oncogenic responses in the rat were observed
in two separate studies reviewed by the Agency.
Because tumors in rats were observed at several sites in
both sexes of two separate studies, there were a large number
of possible approaches to a quantitative risk assessment. The
result of using various data sets and combinations are shown
in Table 5. The QI* is a parameter of the linearized multistage
extrapolation model. It is used as a multiplier of the estimated
exposure (in units of mg/kg/day) to obtain the estimated 95%
upper bound on risk. A change in the Q]_* will result in a
proportional change in risk.
The entries of Table 5 show that the choice of the data
set from among those available for rat oncogenicity makes little
difference in the risk estimate. With one exception, the range
of the Q!*S shown in that table is less than an order of
magnitude.
The GI*'S actually used to produce the upper bound risk
estimates are 5 x 10~2 (for male nasal turbinate tumors in
the second study without the high dose) and 1 x 10 (for the
corresponding data set for females.) Several other possible
approaches were carefully considered by the Agency and are
also discussed in this section.
16
-------
0 The Agency's proposed Guidelines for the Evaluation of
Oncogenicity (EPA, 1984) recommend pooling the incidence of
tumors showing significant elevations for quantitative risk
assessment purposes. In the case of the data set used for
extrapolation (second study without the high dose), the
pooling of tumors results in a change in the status of only
one animal, a male rat with a stomach tumor at the 2.5 mg/kg
dose. The change in the status of this animal caused an
increase in the Qj* from 5 x 10~2 to 1 x ID"1 for males (see
Table 5). The very fact that this two-fold change resulted
from a change in status of only one animal illustrates the
instability of quantitative risk estimates within a twofold
range. This range is well within the uncertainty generally
associated with all risk assessments. It is also within the
range of QI*'S used for the risk estimates presented in this
document. Therefore, using pooled tumor types would have
virtually no effect on the risk estimates.
0 The first alachlor rat study provided results qualitatively
similar to those produced in the second study. The two
studies differed quantitatively, however, as discussed in
Chapter II.A.6. The second study is considered the more
appropriate for risk assessment because it was conducted
with the current technical alachlor mixture and because it
was designed and conducted with knowledge that nasal tumors
were likely. The Agency considered combining the results of
these two studies and the effect of doing so is shown in
Table 5. The range of upper bound risk estimates would vary
less than two-fold from the range given in the risk tables
presented in this document. Since the upper bound risks are
presented as order of magnitude ranges, this degree of difference
makes no meaningful difference in the risk ranges discussed
in this document.
0 As previously noted, the additional dose level (126
mg/kg) was used in the second chronic rat study for the
purpose of investigating the reversibility of eye lesions
previously observed in the earlier rat study. Because of the
criterion employed in assigning animals to the various subgroups
in this study (discussed in Chapter II.6. of this document),
this dose level is not considered fully appropriate for
quantitative risk assessment. However, if it were included,
the effect would be a slight increase the Qj* for males and a
decrease for females (less than two-fold), leaving a range
similar to, but somewhat less than that actually used by the
Agency. As discussed above, this variation is well within the
range of uncertainty generally associated with quantitative
risk assessment.
Table 5 also illustrates the effect of combining or
separating the tumor incidences observed in males and females.
17
-------
Table 5. Q^* Potency Estimates for Alachlor Based on Rat Tumor Data
Nasal Turbinates
Males Females
4
9
5
6
5
x 10-2 1 x
x ID"2 7 x
x 10-2 1 x
x 10~2 3 x
x 10-2 2 x
10-2
10-2
10-1
10-2
10-2
Combining
Program
InPut
2 x 10-2
8 x 10-2
6 x 10-2
4 x ID'2
3 x 10-2
Turbinates,
Sexes
Geometric
Mean
2 x 10-2
8 x 10-2
8 x ID'2
4 x 10-2
4 x 10-2
Stomach or
Male Thyroid
(Follicular M/Ca)
Combining Sexes
Study
Data
First Study
Second Study
Second Study
without High
Dose
Combined
Studies
Combined
without
second
study
High- Dose
Males
3 x 10-3
1 x 10-1
1 x 10-1
6 x 10-2
5 x 10-2
Females
2 x 10-2
1 x 10-1
1 x 10-1
4 x ID"2
4 x 10-2
Program
Input
2 x 10-2
1 x ID-1
9 x 10-2
5 x 10~2
4 x 10-2
Geometric
Mean
2 x 10~2
1 x 10-1
1 x 10~1
5 x 10-2
5 x 10-2
18
-------
The combination of data for sexes may be done in either
of two ways. First, when data sets for both sexes are
essentially equivalent, the data sets are entered together into
the computer program and the combined result yields a flattened
slope as a result of the increased sample size. Second, when
there is some meaningful difference in the dose response patterns
displayed by the sexes, the calculation of the geometric mean
of two or more QI*S is appropriate. Table 5 presents potency
estimates using both of these approaches for each data set
(program input and geometric mean, respectively).
Table 5 thus illustrates 40 different approaches to the
risk extrapolation from the chronic rat studies to man. It can
be readily seen from Table 5 that the use of other subsets of
the data yield potency estimates which are similar to that
derived from the use of the second chronic study excluding the
126 mg/kg dose level. For example, potency estimates derived
from both studies and all dose levels combined are 6 x 10~2
(males) and 3 x 10~2 (females). In fact, all potency estimates
are within a fairly narrow range.
The risk tables which follow in this document present the
range of upper bound estimates of excess cancer risk generated
by extrapolation from tumor rates for both males and females in
the second rat oncogenicity study without the high dose (i.e.
using doses of 0, 0.5, 2.5 and 15 mg/kg). The upper end of the
range represents extrapolation from nasal turbinate tumors in
females as well as extrapolatyion from the combined tumor totals
(nasal turbinate, thyroid and stomach) of either sex, i.e.
these approaches yield identical potency estimates. The lower
end of the range represents extrapolation from the incidence of
nasal turbinate tumors observed in males.
C. Exposure Assessment
The principal routes of exposure to alachlor for the
general population are via the diet and drinking water. Exposure
to users and applicators are also examined below.
1. Dietary Exposures
a. Residues from Treated Raw Agricultural
Commodities "~~
Alachlor is registered primarily for preemergence use on
beans (dry), corn, cotton, lima beans, peanuts, peas, sorghum,
soybeans, sunflowers, and woody ornamentals. Tolerances for
alachlor have also been established for eggs, milk, and the
fat, meat, and meat byproducts of cattle, goats, hogs, horses,
poultry, and sheep. The residue levels permitted under the
alachlor tolerances include residues of alachlor per se plus
selected metabolites.
19
-------
The metabolism of alachlor in plants is generally under-
stood. Residue data indicate that alachlor is absorbed by
corn, cotton, peanut, and soybean plants from treated soil
(Monsanto, 1967 and 1969). Data from a 14C labeled metabolism
study in plants indicate residues are translocated throughout
the entire plant. However, a recent l^C labeled metabolism
study (Monsanto, 1983b) indicated that only 10% and 8%,
respectively, of the total soybean l^c foliar and bean
residue may be detectable by the analytical method presently
used for enforcement purposes (Kovacs, 1984). The enforcement
method may detect only those residues which are converted to
2,6-diethylaniline following the acid hydrolysis step. In
the same study, 50% and 30%, respectively, of the total
soybean foliar and bean l^c residue was discovered to be
converted to 2-ethylaniline following acid hydrolysis. The
remaining activity was either unextractable, unidentified or
arose from radioactive impurities in the applied dose. None
of the latter residues have been shown to be detectable by
the current enforcement methodology. For these reasons the
registrant has been required via the Registration Standard to
furnish data which demonstrate the ability of the present
enforcement method to detect metabolites convertible to
2-ethylaniline or, if that is not possible, to develop an
analytical methodology which could determine metabolites of
alachlor that can be converted, following acid hydrolysis, to
2-ethylaniline in addition to those converted to 2,6-diethyl-
aniline (Zager and Loftus, 1984).
In light of the limits of the present methods of analyzing
for significant levels of alachlor metabolites, the actual
measured residue levels and/or the tolerances established to
limit the maximum residue level may be lower than appropriate.
The metabolism of alachlor in domestic animals is not well
understood at this time and the levels of residues of concern
in domestic animals and their byproducts cannot be fully ascer-
tained. In particular, it has not been demonstrated whether
the residues in animals do indeed contain only the 2,6-diethyl-
aniline moiety. The previously submitted cattle and swine
feeding studies were conducted at IBT and are considered invalid
In the recently submitted goat and laying hen 13C/14C labeled
feeding studies (Monsanto, 1984b and 1984c), the identity of
the residues was not determined. In addition, the reliability
of the studies is questionable. The data reflect only one
feeding level (5.4 ppm for goats and 9.2 ppm for hens) and a
short duration of feeding (5 days for goats, 6 days for hens)
(Dodd, 1984a and 1984b). Therefore, animal metabolism/feeding
studies using both poultry and ruminants have been required as
a condition for any period of continued registration and are
expected to be submitted in the fall of 1984.
20
-------
The maximum expected dietary intake of alachlor residues
by poultry and swine is 0.2 ppm of alachlor in feed based on
the consumption of corn grain and soybean meal in any combination.
Based upon the available information, the maximum expected
dietary intake of alachlor by cattle (meat and dairy) would be
3 ppm if the diet consisted solely of peanut forage and hay.
A more realistic diet would consist only of 60% peanut hay and
40% corn grain which would result in a maximum expected dietary
intake of 1.9 ppm. These estimates of alachlor residue levels
are based on the detection of parent compound and the metabolites
containing the 2,6-diethylaniline moiety only. Recently
submitted plant metabolism studies indicate that a significant
portion of plant residues, particularly in soybeans, consist
of metabolites convertible upon acid hydrolysis to 2-ethylaniline.
Therefore, estimated dietary intakes may actually underestimate
livestock's dietary burden. In any event, these dietary burdens
cannot be extrapolated to residues in meat and milk without
adequate analysis of the metabolism of alachlor (and its meta-
bolites) in the animal. In addition, the enforcement method
does not appear to detect residues convertible to 2-ethylaniline.
The metabolites convertible to 2-ethylaniline are significant
in plants and may be important in meat, milk, poultry and eggs
as well.
Estimates of dietary exposure are presented in the following
table using the standard EPA "food factor" system to estimate
levels of each food item in the typical diet (Schmitt, 1977).
The first column in Table 6 indicates dietary exposure assuming
that all commodities contain residues of alachlor at the tolerance
level. The second column presents dietary exposure for corn,
beans, peas, potatoes, cottonseed and peanuts using the best
available estimate of residues which are the maximum reported
residue levels from actual field trials reflecting the maximum
registered use rates (currently up to 8 Ibs/acre) and are, in
most cases, less than the tolerance levels. These residue levels
are the maximum observed residues using the present enforcement
method of analysis. The Agency recognizes that the actual use
rates are frequently less than the maximum registered use rates.
However, the available data do not indicate lower residues
resulting from lower than maximum use rates. Due to the lack
of appropriate data for sunflowers, sunflower seeds are assumed
to contain residues at the tolerance level. As explained
above, these estimates do not include residues convertible to
2-ethylaniline upon acid hydrolysis and thus may underestimate
the actual dietary exposure to alachlor and relevant metabolites.
21
-------
Table 6. Dietary Exposure to Alachlor and Metabolites
Convertible to to 2,6-Diethylaniline Upon
Acid Hydrolysis
Crop
Theoretical Maximum
Residue Contribution
Tolerance Dietary Exposure
(ppm) (mg/kg/day)
corn
soybeans
beans (dry,
edible)
beans (Lima)
peas
potatoes *
cottonseed
oil
peanuts
sorghum
sunflower
seed
milk &
dairy
meat &
poultry
eggs
TOTAL
0.20
0.20
0.10
0.10
0.10
0.10
0.05
0.05
0.10
0.25
0.02
0.02
0.02
1
5
8
5
2
1
2
5
8
2
1
7
1
6
X
X
X
X
X
X
X
X
X
X
X
X
X
X
10~4
10-5
10-6
ID"6
10-5
10-4
10~6
10-6
10-7
10~6
10-4
10-5
10~6
10-4
Best Available Estimate
Tolerance or
Actual Residue
0
0
0
0
0
0
0
0
0
0
0
0
0
.05
.09
.09
.08
.10
.08
.02
.02
.05
.25
.02
.02
.02
Dietary Exposure
(mg/kg/day)
3
2
7
4
2
1
7
2
4
2
1
7
1
4
X
X
X
X
X
X
X
X
X
X
X
X
X
X
10-5
10-5
10-6
10-6
10-5
10-4
10-7
ID"6
10-7
10-6
10-4
10-5
10-6
lO-4
* The potato use has been discontinued. Removal of the the contribution
from potatoes would reduce the total TMRC to 5 x 10"4 mg/kg/day and
the total Best Available Estimate to 3 x 10"4 mg/kg/day.
22
-------
EPA has evaluated dietary exposure using the more sophisti-
cated assessment of dietary behavior contained in the Tolerance
Assessment System (TAS). The new system was described in the
Agency's "Ethylene Dibromide (EDB) Scientific Support and
Decision Document for Grain Milling and Fumigation Uses" on
February 8, 1984. The estimates used in the system rely on an
extensive data base including the individual 3-day dietary
behavior of 30,770 persons surveyed by the U.S. Department of
Agriculture. For the typical United States consumer, use of
the TAS assessment method did not substantially alter the
estimated dietary exposure.
TAS also permits estimation of dietary burdens of alachlor
from treated crops for population subgroups, as shown in Table
21 (see Chapter II.D.I.a. These estimates utilize the best
available residue estimates in contrast to the use of the
tolerance limit in every use. The average for the total (48
state) population is only slightly different from the
corresponding estimate based upon the standard food factors.
Analysis of dietary exposure patterns using the new TAS
indicates a relatively uniform distribution to the general
population which suggests that a large number of individuals
have similar exposure patterns. This is borne out in the
examination of data for various subgroups which indicates
similar exposure patterns for each region, ethnic group and
season. However, there are important differences in exposure
with respect to the age subgrouping. This table shows non-
nursing infants to have the highest dietary burden. Children
less than 12 years old are also found to have greater than
average exposure. The infant diet (which contains a high
proportion of soybean products) obviously lasts for only a
short portion of any individual's lifetime. The risk estimate
which assumes lifetime exposures associated with that diet
must therefore be regarded as a worst case.
b. Exposure Through Drinking Water
The Agency is concerned about the finding of alachlor in
both surface waters and ground water which are the sources of
drinking water. These findings, particularly the occurrence
of alachlor in municipal water supplies in Ohio, reflect an
additional source of human exposure to alachlor.
Alachlor can enter water systems either by runoff from
agricultural fields into surface water or by leaching downward
through soil to ground water. Although alachlor is biologi-
cally degraded in soil, it does not readily degrade once it
reaches aquatic systems. The tendency for alachlor to leach
is lessened because of biological degradation in soil, but in
areas with little biological activity or with fast recharge
to ground water, such as through fractured soil, alachlor may
be transported to ground water aquifers.
23
-------
The U.S. population of about 231 million people obtains
its drinking water from either public or private water supplies,
which are derived from both ground and surface water sources.
Public water supplies provide water for between 191 to 217
million people and 66% of these people use drinking water
from surface water sources such as rivers, lakes, and reservoirs
and 34% from ground water. The rest of the population, which
does not use public water supplies, obtains drinking water
primarily from private wells.
I. Exposure through Drinking Water from
Ground Water Sources
The likelihood that an agriculturally-applied pesticide
will leach below the unsaturatea root zone to the saturated
zone and eventually appear in ground water and drinking water
is dependent on several factors. Two important factors involve
the persistence and mobility of the pesticide. The rate of decay
in the soil environment is obviously important; the more rapidly
decaying pesticides are less likely to leach than do the more
persistent pesticides. Solubility and the soil binding nature
of a pesticide are also important in determining its potential
to leach. A common measure of the latter is the soil partition
coefficient, K^, which is the ratio of pesticide quantity
adsorbed to soil to that quantity dissolved in water.
In a recent comprehensive review of the leaching of agri-
cultural pesticides to ground water, Cohen et al . (1984)
concluded that pesticides have a potential to leach when the
soil half-lite is greater than 2-3 weeks, the solubility is
greater than 30 ppm, and the Kd is less than 5. For alachlor,
soil half-lite values are in the neighborhood of 3 weeks, the
solubility is 240 ppm, and reported K^ values are in the
range of 0.6-8.1, depending on soil type, with most values
less than 4.0. Pesticides applied to sandy soils have a much
greater chance of leaching tor two reasons: more water leaches
through a sand soil than through other soil types, and K^
values of pesticides on sand are typically lower due to low
organic matter and low clay content tor binding sites.
The method of application is also an important factor of
leaching. Soil incorporation tends to increase the leaching
potential relative to surface or foliar application. Other
factors include soil and air temperature (pesticides which
biodegrade do so more slowly in cooler temperatures), rainfall
near the time of application, geography (weather and soil
patterns), and rate of pesticide application.
Table 7 summarizes available data on alachlor found in
ground water. The data show that alachlor has been found
in well water at levels ranging from 0.01 to 16.6 ppb in three
states and in Ontario, Canada. Higher levels observed in
24
-------
Ontario (Frank, 1984) were determined to be the result of
spills. Areas tested in Nebraska were known to have sandy
soils and shallow, unconfined aquifers, and to be corn-growing
areas (Spalding et al, 1984). The route to wells in the three
Iowa counties was through normal infiltration and also through
runoff and interflow to karst sinkholes followed by rapid
infiltration.
Mathematical models can be used to predict pesticide
transport through the unsaturated zone to the saturated zone
and to determine the potential of a pesticide leaching and
eventually contaminating ground water. One such model is the
Pesticide Root Zone Model (PRZM), which was developed at the
U.S. EPA Environmental Research Laboratory in Athens, Georgia
(Carsel et al.r in press). It is a one-dimensional, time-
varying model for evaluating pesticide fate and transport in
the unsaturated soil zone. A field validation study was initiated
in 1983 by EPA to evaluate the ability of PRZM to predict
actual pesticide movement through soils. The five-year
study will collect field data of pesticide leaching for comparison
to model predictions.
25
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Table 7. Summary of Data on Alachlor in Wells
Location
Positive Samples
Total
Cone.(ppb):mean
positives,range
Comments
Ontario,
Canada
(Frank, 1984)
Ontario,
Canada
(Frank, 1984)
Nebraska
( Spalding
et al., 1980)
Devonian-
Carbonate
Aquifer, Floyd
and Mitchell
Co. Iowa(Libra
et al., 1984)
Big Spring
Basin,
Clayton
County,
Iowa
(Hallberg et
al, 1983)
Maryland
(Maryland
DHMH, 1983)
10
28
8
153
2
14
8/93
3/35
1/59
4/5
4/30
2.1, 0.01-9.1
147, 0.6-780.0
.04, .018-. 071
8.3, 0.10-16.6
.09, 0.05-0.15
.05
5.1, 0.3-12.7
0.4, 0.1-0.8
rural well water;
1979-1984 tests;
all positive wells
were shallow
rural well water
1979-1984 tests;
7 of 8 were result
of spills
Central Platte
Region; 1-2 m silt
loam above sand and
gravel; nitrate found
major findings in
Incipient Karst well;
water level is 3-5 m
below surface
groundwater discharge
into Big Spring
study area wells
surface water
draining into
sinkholes
wells located in
agricultural areas
reflecting statewide
distribution
26
-------
The PRZM model was utilized in two ways to determine
the leaching potential of alachlor. In one, the methodology
known as LEACH (Leaching Evaluation of Agricultural Chemicals:
A Handbook) was used (Dean et al.,1984). In LEACH, the
potential for leaching is expressed as the percentage of applied
pesticide which leaches below the root zone of the crop plotted
against percentage of time. Results of this exercise are
found in Table 8.
The methodology uses PRZM runs simulating 25 years of use
in 11 geographical regions (seven corn sites and four soybean
sites). An important factor in evaluating these results is
that the root zone for corn is 90 cm deep and the root zone
for soybeans is 45 cm; alachlor would have to travel twice as
deep to leave the corn root zone in contrast to the soybean
root zone. Alachlor showed little potential to leach below
the root zone in corn sites. The greatest potential for such
migration was shown in Site 13, which is represented by South
Carolina, but also encompasses North Carolina and Georgia.
As much as 3% of applied alachlor is predicted to leach 10% of
the time (or 1 year in 10). Site 13 was the southernmost site,
and this result reflected the greater amounts of rainfall and
the more intense spring rainfalls in the South as compared to
the North. Soybean sites showed more potential for leaching,
although again this was due to the shallower root depth of
soybeans. Sites 15 and 17, again in the southernmost states,
showed the most potential. In Site 15, as much as 8% of the
applied would leach 10% of the time, and, in Site 17, as much
as 15% of the applied would leach 10% of the time.
The second exercise involved the use of PRZM itself to
evaluate the leaching potential of alachlor when applied to
corn in Iowa and soybeans in Indiana. As seen in Table 9,
PRZM simulations on corn and soybeans showed results comp-
arable to LEACH results. Less than 0.01% of the applied alachlor
was predicted to leach below the corn root zone in Iowa, but
the simulation predicted that 4.6% would leach below the
soybean root zone. However, less than 0.01% was predicted to
leach below two meters for either crop.
The PRZM model assumes a horizontally uniform soil pro-
file. It cannot simulate the occurrence of leaching through
sinkholes, fractured clay layers, or other heterogeneous soil
horizons. Monitoring data verify that these features can
significantly affect the occurrence of pesticide residues in
ground water.
In summary, it can be stated that alachlor has demonstra-
ted a potential to leach. As seen in Table 7, alachlor has
been found in wells, and the causes of these findings have
27
-------
ranged from accidental spills to seepage through sinkholes to
infiltration through soil from normal agricultural use. Further,
model simulations with the PRZM model show that alachlor has the
potential to leach below soybean root zones, and to a lesser
extent, below corn root zones, which reinforces the limited
monitoring data.
28
-------
Table 8. Results of LEACH Analysis
Percent of Applied Alachlor Estimated
to Leach Below Root Zone*
s
I
I
Representative
ite State
. Corn
7
8
9
10
11
12
13
I . Soybeans
14
15
16
17
CO
NE
IL
MI
OH
MD
SC
IA
MS
IN
SC
Percent of applied alachlor
leaching below root zone for
listed percent of time
5%
1-2
0
<1
1
1
2-3
1-3
1-5
5-9
3-5
6-18
10%
<1
0
0
<1
1
1-2
1-3
1-4
4-8
2-4
5-15
50%
0
0
0
0
<1
<1
0-1
0-2
3-5
1-3
4-8
corn root zone = 90 cm; soybean root zone = 45 cm
Table 9. Summary of PRZM Results for Alachlor
Applied to Corn in Iowa and Soybeans
in Indiana
Description
Corn - Iowa
Soybeans - Indiana
1. Percent of applied
alachlor leaching
below root zone, %
2. Percent of applied
alachlor leaching
2 meters, %
3. Average peak soil
water concentration
of alachlor at 2
meters, ppb.
<0.01
<0.01
<0.5
4.6
<0.01
<0.5
29
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II. Exposure through Drinking Water from
Surface Water Sources
A. Monitoring Data
Monitoring data for alachlor in surface water are shown
in Tables 10 and 11. Table 10 contains a summary of monitoring
data extracted from a number of reports which are referenced
in the table. In addition, Table 11 contains a summary of
alachlor monitoring data extracted from the STORET data
base, a publicly-accessible data base maintained by EPA
(U.S. EPA, 1982). Alachlor concentrations in drinking water
(tap water) are shown in Table 12.
The mean concentration (ppb) was calculated as a simple
arithmetic mean of all samples. An individual sample was
either a daily sampling or one of multiple samples collected
in a day. The value of 0.00 was assigned to samples where
alachlor concentration was less than the limit of detection
of the analytical method. Generally, the limit of detection
of the analytical method for alachlor in water is 0.15-0.25 ppb,
although lower limits have been obtained in individual studies.
The mean concentration is not necessarily an average daily or
seasonal exposure, but simply an average of the measurements
which were taken.
To highlight some of the data, surface water monitoring
studies in several rivers in northwestern Ohio show the presence
of alachlor at all sampling stations at most of the sampling
times, which were during the summer months of 1981-1984 with
peak concentrations occurring consistent between late May and
early June. The areas where these monitoring studies were
carried out are dominated by corn and soybean production. In
general, the highest pesticide concentrations were found in
the rivers during the first major runoff events following
spring planting. The findings of alachlor residues in surface
waters two months after spray-time applications is evidence
that alachlor persists in streams or persists in fields for
subsequent runoff.
In 1983, simultaneous monitoring of the Maumee and Sandusky
rivers and tap water from three municipal water supplies deriving
their water from these rivers showed average alachlor levels of
1.24 and 3.11 ppb in the rivers and 0.22, 1.08 and 1.87 ppb in
tap water during the period from May 28 to July 27. The data
indicate that alachlor is not removed by conventional water
treatment processes which do not include carbon filtration.
Less than 1% of the wells, both public and private, which supply
drinking water in the United States are equipped with carbon
filtration. None of the municipal water supply systems in the
United States are equipped with carbon filters, although some
use activated carbon powder for removal of disagreeable taste
and odors.
30
-------
The peak concentrations in surface water (e.g., 267.7 ppb
at Four-Mile Creek (Iowa) Watershed Site #4 and 104.6 ppb at
Defiance) were accountable to runoff events. High pesticide
concentrations in runoff are due to high soil-moisture content
of soil at the site during rain following the application of
alachlor in the spring and summer months. The concentration
of alachlor in runoff depends on the intensity and magnitude
of rainfall and amount of alachlor present in the field during
a rainy day.
31
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Table 10. Alachlor in Surface Water
State Sampling Site
t Positive Peak Cone. Date of Mean Cone. Sanpling
Total (ppb) Peak Cone. (ppb)V Period
OHU981) Honey Creek, 121/158
(Baker et Melmore
al, 1981) Honey Creek, 4/5
Tiro
Upper Honey Creek 42/46
Bean Creek, 8/12
Powers
Ottawa River, 5/10
Allentown
Rocky River, 1/5
Berea
Sandusky River,
Tindell 16/17
Sandusky River,
Mexico 2/2
Sandusky River,
Defiance 28/30
Wolf Creek, 3/3
East Br
Wblf Creek, 3/3
West Br
Maumee River,
Waterville
OH(1982) Maumee,
(Baker, Bowling Green
1983b) (6,313 mi2)
Sandusky,
Fremont
(1,251 mi2)
Raisin River,
Monroe, Mi
1/1
45/53
45/51
21/25
57.0 6/9 5.48 3/30/81-9/7/81
3.87 6/9 1.13 6/9/81-9/7/81
75.6 6/9 10.08 5/4/81-/9/7/81
32.7 6/9 3.79 3/31/81-7/7/81
14.2 6/16 3.18 3/31/81-7/7/81
0.035 5/20 0.01 3/31/81-5/20/81
42.5 6/11 10.29 5/26/81-9/7/81
0.455 9/7 0.30 6/4/81-9/1/81
104.6 6/8 10.94 5/29/81-7/6/81
67.7 6/9 29.26 6/9/81-6/14/81
54.1 6/9 27.74 6/9/81-6/14/81
6.97 6/16 - 6/16/81
9.27 5/28 1.88 12/8/81-8/23/82
18.19 5/29 4.16 12/7/81-8/23/82
8.16 5/29 1.71 4/5/82-8/28/82
1 A value of 0.00 was assigned to samples where alachlor was not detected.The
mean concentration is a simple arithmetic mean of all samples analyzed.
32
-------
Table 10. Alachlor in Surface Water (cont'd)
State Sampling Site # Positive Peak Cone. Date of Mean Cone. Sampling
Total (ppb) Peak Cone, (ppb)l/ Period
OHU982)
(Baker,
19835)
OHU983)
(Baker,
1983b)
(1,042 mi2)
Honey Creek,
Melmore
(149 mi2)
Cuyahoga
(707 mi2)
Lost Creek,
Defiance
(4.4 mi2)
Sandusky,
Fremont
(1,251 mi2)
Maumee,
Bowling Green
(6,313 mi2)
56/65
8/24
41/51
75.0
0.60
18.46
5/24
7.99 12/7/81-8/23/82
7/19 0.07 12/7/81-8/23/82
5/22 0.83 12/8/81-8/23/82
1.24 5/28/83-7/27/83
3.11 5/28/83-7/27/83
OHU984)
(Baker,
1984b)
Rock Creek
Maumee River,
Bowling Green
Sandusky River,
Fremont
Sandusky River
Defiance
Honey Creek,
Melmore
Raisin River
Cuyahoga River
(urban
watershed)
40/54
43/52
46/54
7.42 5/21/84 1.21 4/3/84-7/24/84
18.35 5/24/84 4.38 4/2/84-7/30/84
9.10 6/28/84 2.22 4/2/84-7/30/84
4/2/84-7/30/84
4/2/84-7/30/84
4/8/84-7/29/84
0.07 4/24/84-7/23/84
35/39
57/65
13/17
5/14
33.11
22.89
5.03
0.35
5/21/84
7/7/84
5/27/84
7/23/84
4.58
2.92
0.70
0.07
1 A value of 0.00 was assigned to samples where alachlor was not detected.The
mean concentration is a simple arithmetic mean of all samples analyzed.
33
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Table 10. Alachlor in Surface Water (cont'd)
State
(Miltner,
1984)
OH
(Columbus)
(Binder,
1984: Raw
Water
Intake)
IA
(Johnson
et al. ,
1982,
Sampling Site # Positive
Total
Sandusky River, 17
Tiffin
Sandusky River, 7
Fremont
Maumee River, 20
Bowling Green
Dublin Road,
water plant (raw) 8/8
Dublin Road
water plant(raw) 11/11
Dublin Road
water plant (raw) 7/7
Dublin Road water plant
DRWP Intake 4/4
Griggs Reservoir 4/4
Griggs Reservoir 3/3
0 ' Shaughnessey 4/4
Reservoir
O1 Shaughnessey 3/3
Morse Road water plant
MRWP Intake 4/4
Alum Creek 4/4
Reservoir
Alum Creek 3/3
Reservoir
Hoover Reservoir 4/4
Hoover Reservoir 3/3
Other Samples
Bokes Creek 1/1
0' Shaughnessey
Top 1/1
O' Shaughnessey
Bottom 1/1
O1 Shaughnessey
LLYC 1/1
Four Mile 27/145
Creek 4/86
Watershed 45/130
Site 4 205/222
101/104
Peak Cone.
(ppb)
13.7
5.5
12.2
5.71
6.10
3.65
0.45
0.48
5.76
0.51
5.07
0.25
0.52
0.95
0.40
0.41
7.83
4.05
6.33
3.57
9.60
0.30
54.50
267.70
208.70
Date of
Peak Cone.
6/27/84
5/21/84
5/25/84
6/30/81
6/11/82
7/14/83
1/82
1/82
6/26/83
1/82
6/26/83
10/81
10/81
6/26/83
10/81
8/29/83
6/22/83
6/27/83
6/27/83
6/26/83
5/29/76
5/22/77
6/19/78
6/4/79
6/15/80
Mean Cone. Sampling
(ppb)1/ Period
5.4 5/21/84-7/9/84
3.4 5/18/84-6/25/84
3.6 5/15/84-7/16/84
1.19 6/30/81-1/11/82
3.18 6/10/82-7/21/82
3.23 7/14/83-8/16/83
0.26 10/81-1/82
0.31 10/81-1/82
2.14 6/26/83-8/29/83
0.37 10/81-1/82
1.84 2/12/83-8/29/83
0.20 10/81-1/82
0.42 10/81-1/82
0.79 2/12/83-8/29/83
0.35 10/81-1/82
0.35 2/12/83-8/29/83
6/22/83
6/27/83
6/27/83
6/26/83
1.77 5/2/76-9/19/76
0.01 4/10/77-10/1/77
2.32 5/1/78-9/14/78
5.55 5/1/79-10/29/79
20.27 5/8/80-8/11/80
Clayton Big Spring
County (surface water)
(Hallberg
et al., 1983)
9/9
20.00 6/8/82
2.86 2/24/82-12/29/82
34
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Table 11. Alachlor in Surface Water
Stations Reporting Alachlor Greater Than 2 UG/L in STORET
State Sampling Site Positive
AK
IO
KS
MD
MI
OH
PA
VA
Little River
Chariton River
Big Blue River
Marmaton River
Walnut River
Wakarusa River,
below Clinton Dam
Wakarusa River
near Topeka
Soldier Creek
Octoravo Creek
Raisin River
Maumee River
Sandusky River
Honey Creek
West Conewago Creek
Blackwater Creek
Total
7/39
22/28
13/25
1/5
1/16
1/9
0/3
1/18
4/4
21/23
47/51
45/49
56/60
4/4
1/1
Peak Cone,
(ppb)
2.1
101.0
3.2
4.2
2.4
3.2
0.0
4.4
2.7
8.2
9.3
18.0
70.0
11.0
3.4
Date of Mean Cone ,*Sampiing
Peak Cone. (ppb) Period
6/9/76
7/19/78
6/16/82
7/7/82
12/19/82
5/7/78
—
7/13/82
6/4/81
5/29/82
5/28/82
5/29/82
5/25/82
6/4/81
5/23/79
0.08
12.58
0.68
0.91
0.25
0.25
0.0
1.87
—
1.86
1.99
4.43
5.93
3.92
2.0
3/76-10/82
5/78-7/78
6/78-9/83
7/79-7/83
12/78-10/78
1975-1978
9/82-9/84
4/79-7/83
6/81-9/81
4/82-8/82
12/81-8/82
12/81-8/82
12/81-8/82
6/81-9/81
5/79
* A value of 0.00 was assigned to samples where alachlor was not detected.
The mean concentration is a simple arithmetic mean of all samples
analyzed.
35
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Table 12. Alachlor in Tap Water
State Sampling Site Positive
Total
Peak Cone. Date of Mean Cone. Sampling
(ppb) Peak Cone. (ppb) Period
OH
6/6
6/6
3/5
Tiffin (Ohio EPA,
Baker 1983a)
Tiffin (Baker et
al 1981)
Tiffin (Baker,
1982)
Fremont (Baker,
1983b)
Bowling Green
(Baker, 1983b)
Tiffin (Baker,
1983b)
Columbus
(Binder,
1984) Dublin Road
water plant(tap)
Dublin Road 11/11
water Plant(tap)
Dublin Road 7/7
water plant(tap)
LA New Orleans
(Nat. City
Res. Council,
1977)
6/6
14.0
14.3
11.4
1.10
5.71
3.57
5/25/82
6/17/81
5/28/82
8/3/81
6/11/82
7/14/83
2.9 1977 (Summer)
4.14 5/10/82-7/7/82
5.10 6/4/81-9/1/81
2.45 12/10/81-5/28/82
0.22 5/28/83-7/27/83
1.87 5/28/83-7/27/83
1.08 5/28/83-7/27/83
0.47 6/30/81-1/11/82
2.82 6/1/82-7/21/82
2.39 7/14/83-8/16/83
36
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B. Modeling Assessment
In order to more fully understand the significance of the
available data on alachlor contamination of surface drinking
water sources, EPA has employed a model designed to predict
pesticide concentrations in streams resulting from transport
of the pesticide from field application sites to the stream.
This model, the Hydrologic Simulation Program - Fortran (HSPF),
takes into account the various processes which are likely to
influence the behavior of alachlor in watershed areas, both on
and in the soil and within the stream (Johanson, et al.,
1980) . The model was applied to predict the instream concen-
trations which would be expected in three watersheds where
alachlor is applied to soybeans and corn. The watersheds
reflect a range in the extent of alachlor use and in geographic
and climatic conditions.
Sections 1 and II of Mulkey et al. (1984) provide a fuller
discussion of the properties which influence the movement of
alachlor in watersheds, and the methodology by which the HSPF
model accounts for all the factors appropriate for useful
predictions of pesticide concentrations in streams.
As noted above, HSPF was applied to data from three water-
sheds. The first, the Iowa River Watershed in central Iowa
is located in the heart of the corn belt where about 67% of
the land area is used to grow corn and soybeans. Alachlor is
applied there in late May or early June. The heaviest rainfalls
occur in those months, and annual rainfall is moderate (approxi-
mately 30 inches per year). In the second watershed, the
Little River Watershed in south central Georgia, only about
20% is cropped to soybeans or corn, where alachlor is applied
in mid-March. March, June, July and August are the wettest
months; annual rainfall is heavier (approximately 45 inches).
The third watershed, the Yazoo River is a major stream flowing
into the Mississippi River. The watershed area used for this
study contains about 31% corn and soybean land. Alachlor
use occurs in April which, with December, is the wettest period.
Intense periodic rainstorms and flooding are frequent and
annual rainfall is about 52 inches.
The data and calibrations required for hydrologic simula-
tion with the HSPF model are available for each of these
specific watersheds. Such site-specific data for model simu-
lations are rare. For alachlor, application rates and modes
were taken from label directions and application times were
assumed to be distributed through the time period normal for
each area. Actual field data on pesticide disappearance rates
and dissolved/non-dissolved partitioning were available from
the Iowa area. Those data, supplemented by laboratory data
as necessary, were used to model all three areas, with
adjustments for known effects of temperature differences on
the values. The values for acreage treated were based solely
37
-------
on corn and soybean acreage, because only those crops currently
have extensive alachlor use. For the Iowa River Watershed,
estimates of resulting instream concentrations were derived
by three different approaches to estimate acreage treated
using (1) the results of a site-specific alachlor use survey,
(2) state-wide USDA use data, and (3) a "full treatment"
hypothetical scenario that all corn and soybean acreage would
be treated. In the Little River and Yazoo Watershed areas,
only two approaches, regional USDA use data and the hypothetical
"full treatment" case, were used. A fuller discussion of the
data relied on for this modeling is contained in Section III
and IV of Mulkey et al. (1984). With this HSPF simulation,
it is possible to obtain estimates of instream concentrations
at multiple points along the modeled stream length for any
two-hour period over a ten-year span. Values for daily mean
alachlor concentrations in the Iowa River are estimated for
three locations; in the Yazoo River concentrations were estimated
at two locations; and in the Little River only the concentrations
at the mouth of the study area are estimated. The values for
all of these areas were analyzed to determine the ten-year
annual mean, the ten-year monthly mean in each of the spring/
summer months which constitute the run-off season, and the
ten-year peak daily mean for each year. Table 13 shows the
three Iowa River locations, with annual estimates for each of
the three treatment cases. Table 14 presents the ten-year
averages for the two Yazoo sites, presented annually and by
"high season" months for both treatment cases. Table 15 presents
the ten-year average data for the Little River site. More
complete results and a discussion of the results, including a
comparison to available data on measured alachlor concentrations
are found in Section V of Mulkey et al. (1984).
Several useful conclusions may be drawn from this modeling
effort. In the Iowa River area, average concentrations over a
ten-year period under current use patterns are predicted to be
about 2 ppb. If all corn and soybean acreage in the area were
treated with alachlor, the ten-year average would be greater
than 5 ppb and in high rainfall years the average could reach
10-15 ppb averages for those years. The annual averages
reflect months of zero concentration levels in the stream.
Estimates of concentrations for individual "high season" months
under current use patterns exceed 10 ppb with some frequency
and can exceed 40 ppb. Daily concentrations are estimated
to reach well over 200 ppb. Therefore, estimates of lifetime
exposure based on alachlor contamination of surface water
sources at 2-5 ppb appear realistic for the cornbelt area.
In the Yazoo and Little River areas, by contrast, ten-year
average concentrations appear unlikely to exceed 1 ppb, even
if all corn and soybeans were treated with alachlor. Some
reaches of the Yazoo could see long-term average concentrations
of from 1 to 2 ppb for a "full treatment" use pattern. Generally,
estimates of lifetime exposure based on alachlor contamination
38
-------
of surface water outside the cornbelt area should not use
values exceeding 1 ppb. "Worst case" estimates for the Yazoo
might be appropriate using the 2 ppb average value possible in
maximum rainfall years of full alachlor use.
For risk assessment purposes, these modeling estimates of
alachlor concentrations greatly increase the confidence that
the Agency can place in its estimates of drinking water exposure
derived from the available monitoring data on alachlor conta-
mination of surface drinking water sources and of tap water
taken from those sources. The closeness between modeled and
observed results, the opportunity to consider the effects of
important variables such as rainfall or extent of use, the
geographic and climatic variation among modeled sites, and
the careful model and data development all contribute to the
usefulness of the results.
39
-------
Table 13. Predicted Alachlor Solution Concentrations (ppb)
Iowa River at Marengo - Case I
Year
1969
1970
1971
1972
1973
1974
1975
1976
1977
1978
10-year
Year
1969
1970
1971
1972
1973
1974
1975
1976
1977
1978
10-year
Year
1969
1970
1971
1972
1973
1974
1975
1976
1977
1978
10-year
Annual
Mean Cone.
5.79
0.43
0.93
1.82
0.95
5.08
1.78
1.67
0.28
3.49
mean 2.24
Iowa River
Annual
Mean Cone.
2.67
0.22
0.43
0.84
0.44
2.34
0.82
0.77
0.13
1.61
Mean 1.03
Iowa River
Annual
Mean Cone.
15.11
1.25
2.43
4.75
2.49
13.24
4.64
4.36
0.74
9.11
Mean 5.83
Peak
Monthly
Daily
247.
30.
32.
122.
60.
276.
69.
77.
5.
202.
4
88
66
93
72
76
58
17
29
33
May
44.
4.
3.
0.
8.
39.
1.
7.
0.
21.
13.
at Marengo -
Peak
2
69
43
65
64
91
91
75
89
09
32
June
24.
0.
7.
20.
2.
20.
18.
11.
1.
16.
12.
Case
0
72
16
85
63
05
94
96
97
38
46
II
Mean
July
1
0
0
0
0
0
0
0
0
4
0
Monthly
Daily
114.
14.
15.
56.
27.
127.
32.
35.
2.
93.
at
Peak
01
23
05
65
98
54
11
56
44
24
May
20.
2.
1.
0.
3.
18.
0.
3.
0.
9.
6.
37
16
58
30
98
39
88
57
41
72
14
Marengo -
June
11.
0.
3.
9.
1.
9.
8.
5.
0.
7.
5.
Case
05
33
30
61
21
24
73
51
91
55
74
III
.30
.20
.54
.24
.28
.85
.41
.25
.50
.49
.91
Mean
July
0
0
0
0
0
0
0
0
0
2
0
Monthly
Daily
645.
80.
85.
320.
158.
721.
181.
201.
13.
527.
30
54
18
64
37
88
74
27
81
74
May
115.
12.
8.
1.
22.
104.
4.
20.
2.
55.
34.
29
23
94
70
53
09
98
21
32
02
75
June
62.
1.
18.
54.
6.
52.
49.
31.
5.
42.
32.
54
87
68
39
85
30
41
19
15
.60
.09
.25
.11
.13
.39
.19
.12
.23
.07
.42
Mean
July
6
0
1
0
0
2
1
0
1
73 11
49
2
.26
.51
.42
.62
.74
.21
.08
.68
.30
.72
.38
Aug
0
0
0
0
0
0
0
0
0
0
0
.04
.02
.04
.02
.02
.02
.02
.02
.09
.02
.04
Aug
0
0
0
0
0
0
0
0
0
0
0
.02
.01
.02
.01
.01
.01
.01
.01
.04
.01
.02
Aug
0
0
0
0
0
0
0
0
0
0
0
.11
.06
.11
.11
.11
.11
.11
.11
.23
.11
.11
40
-------
Table 13. Predicted Alachlor Solution Concentrations (ppb)
Iowa River at Marshalltown - Case I
Year
1969
1970
1971
1972
1973
1974
1975
1976
1977
1978
Annual
Mean Cone
4
0
1
1
0
4
2
1
0
2
.99
.24
.17
.39
.87
.45
.02
.39
.43
.47
Peak
Daily
301
7
77
133
86
321
86
99
20
87
.70
.73
.08
.80
.93
.68
.71
.62
.09
.82
Monthly
May
34
1
4
0
8
33
2
8
1
8
.05
.37
.84
.87
.40
.27
.13
.92
.00
.51
Mean
June July
24
1
8
15
1
19
21
7
3
17
.17
.19
.66
.45
.52
.42
.81
.44
.62
.77
1.52
0.17
0.61
0.24.
0.35
0.69
0.24
0.20
0.54
3.52
Aug
0
0
0
0
0
0
0
0
0
0
.02
.02
.04
.02
.02
.02
.02
.02
.09
.02
10-year Mean 1.95
10.33 12.11 0.80 0.03
Iowa River at Marshalltown - Case II
Year
1969
1970
1971
1972
1973
1974
1975
1976
1977
1978
10-year
Annual
Mean Cone.
2
0
0
0
0
2
0
0
0
1
Mean 0
.30
.11
.54
.64
.40
.05
.93
.64
.20
.14
.90
Peak
Daily
139
3
34
61
40
148
39
45
9
40
.03
.56
.52
.66
.06
.24
.96
.91
.26
.47
Monthly Mean
May
15
0
2
0
3
15
0
4
0
3
4
.69
.63
.23
.40
.87
.33
.98
.11
.46
.92
.76
June
11
0
3
7
0
8
10
3
1
8
5
.14
.55
.99
.12
.70
.95
.05
.43
.67
.19
.58
July
0
0
0
0
0
0
0
0
0
1
0
.70
.08
.28
.11
.16
.32
.11
.09
.25
.62
.37
Aug
0.01
0.01
0.02
0.01
0.01
0.01
0.01
0.01
0.04
0.01
0.01
Iowa River at Marshalltown - Case III
Year
1969
1970
1971
1972
1973
1974
1975
1976
1977
1978
10-year
Annual
Mean Cone.
13
0
3
3
2
11
5
3
1
6
Mean 5
.02
.62
.05
.62
.26
.60
.26
.62
.13
.45
.09
Peak
Daily
786
20
195
349
226
839
226
259
52
229
.91
.15
.38
.00
.74
.04
.17
.85
.41
.06
Monthly
May
88
3
12
2
21
86
5
23
2
22
26
.81
.57
.62
.26
.90
.77
.55
.26
.60
.19
.94
Mean
June July
63
3
22
40
3
50
56
19
9
43
31
.05
.11
.58
.30
.96
.66
.88
.41
.45
.36
.58
3
0
1
0
0
1
0
0
1
9
2
.96
.45
.58
.62
.91
.81
.62
.51
.42
.17
.09
Aug
0.06
0.06
0.11
0.06
0.06
0.06
0.06
0.06
0.23
0.06
0.08
41
-------
Table 13. Predicted Alachlor Solution Concentrations (ppb)
Iowa River at Rowan - Case I
Year
Annual
Mean Cone.
1969
1970
1971
1972
1973
1974
1975
1976
1977
1978
10-year
Year
2
0
0
0
0
1
1
0
0
1
Mean 0
.19
.37
.69
.63
.24
.48
.54
.52
.89
.32
.98
Iowa
Annual
Mean Cone.
1969
1970
1971
1972
1973
1974
1975
1976
1977
1978
10-year
Year
1
0
0
0
0
0
0
0
0
0
Mean 0
.00
.17
.32
.29
.11
.68
.71
.24
.41
.61
.45
Iowa
Annual
Mean Cone.
1969
1970
1971
1972
1973
1974
1975
1976
1977
1978
10-year
5
0
1
1
0
3
4
1
2
6
Mean 2
.66
.96
.81
.64
.62
.85
.02
.36
.32
.27
.55
Peak
Daily
120.61
19.42
30.58
69.48
12.80
66.29
81.98
26.79
58.13
74.24
River at
Peak
Daily
55.58
8.95
14.09
32.02
5.90
30.55
37.78
12.18
26.79
34.21
River at
Peak
Daily
314.58
50.66
79.75
181.23
33.39
172.91
213.83
68.94
151.63
193.63
May
11
1
4
0
1
6
2
2
1
5
3
Rowan -
.22
.35
.04
.33
.26
.23
.76
.39
.61
.73
.69
Monthly
Mean
June July
13.48
2.84
3.12
6.77
1.39
10.78
15.54
3.62
7.29
9.27
7.42
1.19
0.17
1.04
0.41
0.30
0.52
0.11
0.09
1.37
0.78
0.61
Aug
0
0
0
0
0
0
0
0
0
0
0
.02
.02
.17
.02
.02
.02
.02
.00
.39
.02
.07
Case II
May
5
0
1
0
0
2
1
1
0
2
1
Rowan -
.17
.62
.86
.15
.58
.87
.27
.10
.74
.64
.70
Monthly
June
6.21
1.31
1.44
3.12
0.64
4.97
7.16
1.67
3.36
4.27
3.42
Mean
July
0
0
0
0
0
0
0
0
0
0
0
.55
.08
.48
.19
.14
.24
.05
.04
.63
.36
.28
Aug
0
0
0
0
0
0
0
0
0
0
0
•
01
.01
•
08
.01
•
•
•
•
•
*
•
01
01
01
00
18
01
03
Case III
Monthly Mean
29
3
10
0
3
16
7
6
4
14
9
May
.26
.51
.53
.85
.28
.24
.19
.23
.19
.94
.62
June
35.15
7.41
8.15
17.66
3.62
28.13
40.53
9.46
19.02
24.17
19.36
July
3.11
0.45
2.72
1.08
0.79
1.36
0.28
0.23
3.57
2.04
1.58
Aug
0
0
0
0
0
0
0
0
1
0
.06
.06
.45
.06
.06
.06
.06
.00
.02
.06
0.19
42
-------
Table 14. Predicted Alachlor Solution Concentrations (ppb)
10-YearPeakMonthly Means ~
Mean Daily May June July Aug.
Yazoo River, MS - Case II
Yazoo R. at Lambert 0.18 23.45 0.04 1.98 0.11 0.01
Yazoo R. at Swan Lake 0.13 21.14 0.03 1.48 0.05 0.01
Yazoo Riverf MS - Case III
Yazoo R. at Lambert 1.25 162.74 0.28 13.74 0.76 0.07
Yazoo R. at Swan Lake 0.90 146.71 0.21 10.27 0.35 0.07
Table 15. Predicted Alachlor Concentrations (ppb)
10-YearPeakMonthly Means
Mean Daily Feb Mar Apr May June
Little River, GA - Case II
Little R. GA. 0.12 14.50 0.00 1.08 0.28 0.04 0.01
Little River, GA - Case III
Little R. GA. 0.56 67.86 0.01 5.05 1.31 0.19 0.05
43
-------
2. Applicator Exposure
Alachlor is applied once per growing season prior to or
immediately after planting. Three groups of applicators are
exposed to alachlor. These are the private farmer, the custom
applicator and the aerial applicator. Approximately 70% of
the alachlor applied per year is applied by the private farmer.
Less than 1% was applied aerially; however, aerial application
of alachlor was voluntarily cancelled by Monsanto.
The registrant has submitted studies which measured worker
exposure to alachlor during aerial and ground applications of
the emulsifiable concentrate, microencapsulated and granular
formulations (Lauer and Arras, 1981). The inhalation and
dermal exposures to the mixer/loader, pilot and flagger were
measured during aerial application and the exposure of the
mixer/loader and applicator was measured during ground
application. Dermal exposure was assessed by measuring residue
deposits on gloves or gauze pads and respiratory exposure was
assessed through the extraction of foam plugs, silica'gel and
charcoal from air samples taken near the breathing zone.
The exposure situation which the Agency considers to be
appropriate for analysis of occupational exposure to alachlor
assumes the worker is wearing protective clothing such as
coveralls and rubber gloves (during mixing and loading).
Protection of this type is assumed to reduce exposure to
covered body areas by about 80% because some pesticide will
penetrate the material or filter in around edges and hems.
Accordingly, the exposure assessment presented in Table 16
uses the Monsanto data conducted with protected workers and
adjusts for exposure to body areas based on this 80% figure.
Inhalation exposure is insignificant compared to dermal
exposure. For example, the exposure figures for a mixer/loader
(ground tank fill) assuming 80% protection are .44 mg/kg/day
for dermal and .00027 mg/kg/day for inhalation. This range
in exposure figures is consistent for each use pattern. The
following three tables, Tables 16, 17 and 18, present exposure
estimates resulting from the use of different assumptions
regarding protective clothing. In Table 17, the worker is
unprotected. In Table 18, the face, back of the neck, front
of the neck and "v" of the chest are exposed, rubber gloves
are worn and the rest of the body is completely protected.
Current occupational exposure to alachlor probably does
not reflect the protections outlined in the two more restrictive
"exposure situations discussed above. Therefore, the occupational
exposure estimates presented in Tables 16 and 18 may underestimate
actual current exposure. However, the protective measures assumed
in Table 16 could be readily and easily required and reasonable
compliance with such requirements seems likely. These are the
requirements to be implemented prior to the 1985 season under
the alachlor Registration Standard.
44
-------
The Agency believes that the exposure estimates presented in
Table 16 are the most relevant for risk assessment purposes.
The Agency also believes that most pilots do not mix/load
pesticides prior to aerial application. Exposure estimates for
pilots and mixer/loaders have therefore not been combined. The
mixer/loader and aerial applicator exposure estimates should be
considered separately. For ground application, the mixer/loader
and ground applicator are usually not the same individual and
those exposure estimates should also be considered separately.
In assessing applicator exposure for oncogenic risk assess-
ment purposes, it is assumed that an individual is exposed for
a 40 year working lifetime during a 70 year lifespan. The
exposure estimate also adjusts for the estimated number of days
per year that an applicator is exposed (1 to 6 days for a
private farmer, 5 to 30 days for a custom ground applicator and
5 to 10 days for an aerial applicator of alachlor) and present
the range in applicator exposure expected from applying a
alachlor at 2 Ibs/acre to 4 Ibs/acre . The exposure (received
over a 40 year working life) is therefore an average of the
exposure level on the exposed days and the unexposed days over
a 70 year lifetime.
The following tables present applicator exposure estimates
for the three degrees of protective clothing discussed previously.
The latter two columns in these tables reflect the range of
exposure taking into account the likely number of days per year
that exposure may occur. All figures assume a 50% dermal
absorption rate with the exception of the microencapsulated
formulation where 12% absorption is assumed. These figures are
based on dermal absorption studies submitted by Monsanto using
human skin and in vivo studies using Rhesus monkeys (Monsanto,
1981a & 1981b).
45
-------
Table 16. Alachlor Worker Exposure (mg/kg/day)
with Protection (80%)*
Use Pattern
Exposure on
Day of Application
Lifetime Average Exposure
By Days of Exposure/Year
1 day/year 30 days/year
Ground Tank Fill
2 x 10"1
2 x 10~2
Ground Applicator
Ground Transfer (Closed System)
5 gal container 2 x 10"2
55 gal container 1 x 10"1
LASSO EC
4 x 10~4
3 x 10~5
3 x icr5
2 x 1CT4
Aerial Application
Tank Fill
Pilot
Flagger
* *
2 x 10~°
1 x 10"1
4 x 1CT1
2 x 10-2
9 x 10~4
3 x 10-3
Other Formulations of LASSO
Micro-Encapsulated
Mixer-Loader
Applicator
Combined
Granular (LASSO II)
Mixer-Loader
Applicator
Comb i ned
8 x ID'2
9 x 10-3
9 x ID"2
1 x ID'1
3 x 10~4
1 x 10"1
1 x 10~4
1 x ID"5
1 x 10~4
8 x 10~4
2 x 10~6
8 x 10~4
1 x 10-2
1 x 10~3
8 x 10~4
5 x 10-3
5 d/year 10 d/year
3 x 10-2
2 x 10-3
5 x 10-2
1 d/year 30 d/year
4 x 10-3
4 x 10~4
4 x 10-3
2 x 10-2
6 x 10-5
2 x 10-2
"* Exposure estimates assume an application rate of 4 Ibs per
acre. Estimated exposure from other rates will be proportional
to the application rate.
**Aerial application has been discontinued.
46
-------
Table 17. Alachlor Worker Exposure (mg/kg/day)
No Protection*
Use Pattern
Exposure on
Day of Application
Lifetime Average Exposure
By Days of Exposure/Year
1 day/year 30 days/year
Ground Tank Fill 1.9 x!0°
Ground Applicator 7 x 10~2
Ground Transfer (Closed System)
LASSO EC
3 x 10-3
1 x 10-4
5 gal container 1
55 gal container 9
Aerial Application**
Tank Fill 9
Pilot 4
Flagger 1
Other
Micro- Encapsulated
Mixer-Loader 1
Applicator 9
Combined 1
x 10°
x 10-1
x 10°
x 10-1
x IQl
Formulations of
x 10-1
x 10"3
x 10-1
2
8
5
7
4
1
x 10-3
x 10-4
d/year
x 10-2
x 10-3
x 10-1
LASSO
1
2
1
1
d/year
x 10-4
x 10~5
x ID"4
Granular (LASSO II)
Mixer-Loader 2 x 10°
Applicator 4 x 10"3
Combined 2 x 10°
4 x 10-3
6 x 10~6
4 x 10-3
9 x 10-2
3 x 10-3
6 x 10-2
4 x 10-2
10 d/year
2 x 10-1
7 x 10-3
2 x 10-1
30 d/year
7 x 10-3
4 x 10-4
4 x 10-3
1 x 10-1
2 x 10-4
1 x 10-1
* Exposure estimates assume an application rate of 4 Ibs per
acre. Estimated exposure from other rates will be proportional
to the application rate.
** Aerial application has been discontinued.
47
-------
Table 18. Alachlor Worker Exposure (rag/kg/day)
With 100% Protection*
Use Pattern
Exposure on
Day of Application
Lifetime Average Exposure
By Days of Exposure/Year
1 day/year 30 days/year
Ground Tank Fill 5 x 10~2
Ground Applicator 1 x 10~2
Ground Transfer (Closed System)
5 gal container
55 gal container
Aerial Application
Tank Fill
Pilot
Flagger
**
I x 10-2
3 x 10-2
1 x ID"1
3 x 10-2
1 x 10°
LASSO EC
8 x 10~5
2 x 10~5
2 x 10-2
5 x 10-5
9 x 10-4
2 x 10~4
9 x 10-3
1 x 10-3
5 x 10"4
6 x 10-4
1 x 10-3
2 x 10~3
5 x 10~4
2 x 10-2
Other Formulations of LASSO
Micro-Encapsulated
Mixer-Loader 7 x 10"2
Applicator 8 x 10"3
Combined 8 x 10~2
Granular (LASSO II)
Mixer-Loader 5 x 10"3
Applicator 7 x 10"4
Combined 1 x 10~2
1 x 10-4
1 x 10~5
1 x ID'4
4 x 10~6
6 x 10~7
1 x 10~5
3 x 10-3
4 x 10"4
3 x 10-3
2 x 10-4
2 x 10-5
2 x IP"4
* Exposure estimates assume an application rate of 4 Ibs per
acre. Estimated exposure from other rates will be proportional
to the application rate.
** Aerial application has been discontinued.
48
-------
The Agency has determined that a substantial number of
workers are exposed to alachlor during application operations.
Most of these workers are exposed during application at rates
of 2 Ib/acre or less. For example, for field corn only about
22% of the applicators are exposed to more than 2 Ib/acre.
Estimates of the number of individuals in each occupational
exposure group are presented in Table 19. The approximately
650,000 private farmers who apply alachlor using ground equipment
and the 650,000 mixer/loaders associated with the same operation
can be exposed to alachlor from 1 to 6 days per year. The
approximately 89,000 custom applicators, and associated mixer/
loaders, using ground equipment can be exposed to alachlor from
5 to 30 days per year. There was limited use of aerial application,
therefore, only about 1000 aerial applicators, 1000 aerial mixer/
loaders and 100 flaggers were exposed for 5 to 10 days per year.
49
-------
Table 19. Estimated Number of Applicators, Mixer-Loaders and Flaggers Potentially Exposed to
Alachlor Herbicide Per Year
Site
Soybeans
Peanuts
Corn
Green Peas
Lima Beans,
Dry Beans,
Kidney Beans,
Mung Beans
Cotton
Sunflowers
Grain Sorghum
Potatoes
TOTALS
Custon Ground
Applicators
1,500
480
87,000
88,980
Private Farmer
Ground
Applicators
408,900
15,500
215,000
210
2,300
150
360
4,300
4,700
651,420
Aerial Custom
Applicators
—
160
880
1,040
Private Farmer
Ground
Mixer/Loaders
408,900
15,500
215,000
210
2,300
150
360
4,300
4,700
651,420
Custom Ground
and Aerial
Mixer/Loaders
1,500
750
87,800
90,050
Flaggers
(Assuming 10%
human, 90%
automatic)
—
20
88
108
50
-------
D. Risk Characterization
The plausible upper limit to the excess cancer risk is
obtained by taking the QI*S from the Dose-Response Assessment
(5 x 10~2 to 1 x lO"1 per mg/kg/day) and multiplying it by the
estimates from the Exposure Assessment. The result is coupled
with estimates of the certainty/uncertainty in the Hazard
Identification and Exposure Assessment to provide a final
conclusion. As previously noted, the Agency has assigned
alachlor to category B2 (a probable human carcinogen) of the
EPA modification of the IARC classification scheme. The risk
estimates in this document should be interpreted in the context
of this classification.
1. Dietary Risks
a. Risks from Consumption of
Raw Agricultural Commodities
Exposure estimates and corresponding risks are presented
in Table 20. As explained in Section II.B., maximum exposure
estimates were developed from tolerances established for residues
of alachlor in foods. It is assumed that residues are present
in all individual raw agricultural commodities to the extent
permitted by the tolerances, e.g. all corn consumed by an
individual has a residue of 0.2 ppm alachlor. It is also
assumed that the total daily diet is 1.5 kg and that the average
body weight is 60 kg. The best estimates were developed based
on available information on residue levels actually measured in
field tests. All exposures in Table 20 were developed using
the EPA food factor system.
Both the TMRC and best estimates, however, may underestimate
exposures to residues of concern because of limitations mentioned
above in the analytical method to detect metabolic products of
alachlor. Note that estimates presented here for total dietary
exposure and risk do not consider exposure through drinking
water.
51
-------
Table 20. Quantitative Assessment of Dietary Risks for Alachlor
Crop
Theoretical Maximum
Residue Contribution
Dietary Exposure
(mg/kg/d)
corn
soybeans
Beans , dry
edible
beans, Lima
Peas
**Potatoes
Cottonseed
(oil)
Peanuts
Sorghum
Sunflower
Milk & Dairy
Meat & Poultry
Eggs
TOTAL
1
5
8
5
2
1
2
5
8
2
1
7
1
6
X
X
X
X
X
X
X
X
X
X
X
X
X
X
1(T4
10-5
10~6
10~6
10-5
10-4
10~6
10~6
10-7
10~6
10~4
10-5
io-nwi n in 4-ho 1 H~5 _ 1 n~4 »-=»nr«a in hv^-h r-acoc
on
remain in the 10
10 q range in both cases.
52
-------
Table 21 contains the exposure and associated upper bound
risk estimates derived from use of the Agency's new Tolerance
Assessment System as discussed in Chapter II.C.I.a. As noted
earlier, the TAS exposure estimates, in general, are similar
to those obtained from the Agency's traditional approach.
Children and infants estimates are different because their
diet is so different from adults. These diets, of course,
are not lifetime exposures and, therefore, need to interpreted
with care. The children's and infant diets would yield the
appropriate exposure estimate if risk is in fact determined
by the level of exposure early in life or by the highest
exposure occurring for any short portion of the lifespan.
It would overstate exposure if the average exposure over a
lifetime is the determining factor for health effects.
There is no way to differentiate between these possibilities
in the animal studies, which have a relatively constant
exposure over the animal's entire lifetime. The chronic rat
study extension, which exposed animals to dose levels of 126
mg/kg/day either for a lifetime or for a quarter of a lifetime,
suggested that early exposure to young animals may contribute
disportionately to the induction of nasal turbinate tumors.
However, this extension of the chronic study was not designed
to investigate the effect of early exposure to alachlor on
induction of tumors. The potential bias in the selection of
animals removed from exposure to alachlor limit the conclusions
that can be drawn regarding the effect of partial lifetime
exposure on tumor induction.
53
-------
Table 21. Estimated Dietary Exposure (mg/kg/day) to Alachlor
from Treated Crops and Corresponding Upper Limits
of Excess Cancer Risks for Population Subgroups^/
Population Subgroup
Estimated
Dietary Exposure
Corresponding
Upper Limit of
Excess Cancer
Risk Estimate
Population:
48 states
(All Seasons)
5 x 10-4
10-5 _ 10-4
Spring
Summer
Fall
Winter
Northeast Region
North Central Region
Southern Region
Western Region
Hispanic
Non-Hispanic Whites
Non-Hispanic Blacks
Non-Hispanic Other
Nursing Infants (less than 1 year)
Non-Nursing Infants (less than
1 year)
Female (13 years or more, Pregnant)
Female (13 years or more, Nursing)
Children (1-6 years)
Children (7-12 years)
Male 13-19 years
Female 13-19 years (not pregnant
or nursing)
Males (20 years or more)
Females (20 years of more not
pregnant or nursing)
4 x 10-4
5 x ID"4
5 x 10-4
5 x 10~4
4 x ID"4
5 x 10-4
4 x 10-4
5 x 10-4
6 x 10-4
5 x ID"4
5 x 10-4
5 x 10-4
4 x 10~4
2 x 10-3
3 x ID"4
4 x 10~4
1 x 10-3
7 x 10-4
5 x 10-4
4 x ID'4
3 x 10-4
3 x 10-4
10-5 _
10-5 _
10-5 _
10-5 _
10-5 _
10-5 _
10-5 _
10-5 _
10-5 _
10-5 _
10-5 _
10-5 _
10-5 _
10-4
10-5 _
10-5 _
10-5 _
10-5 _
10-5 _
10-5 _
10-5 _
10-5 _
lO"4
10-4
10-4
lO-4
10-4
10-4
10-4
10-4
10-4
10-4
10-4
10-4
10-4
10"4
ID"4
10-4
ID'4
ID"4
10-4
ID"4
10-4
T/See text for explanatory note on infant and child risk estimation.
54
-------
b. Drinking Water Risks
As discussed in Chapter Il.C.l.b., there is also a
potential for exposure to alachlor in drinking water. A time
weighted average of 2 to 5 ppb was determined to be a realistic
estimate of exposure from alachlor contaminated surface water
for the cornbelt area. Assuming that a 10 kg child consumes
one liter of water per day and that water contains 2 ppb
alachlor, the alachlor exposure would be 2 micrograms/kg body-
weight/day. If it is further assumed that this is for a life-
time of exposure, a level of 2 ppb would be associated with
an upper 95% bound estimate of lifetime cancer risk of approx-
imately 10-5, A time weighted average of 5 ppb, using the
same assumptions, would result in a range of upper bound risk
estimates of 10"4 to 10"5.
The previously discussed surface water modeling indicates
that occasional yearly averages of 15 ppb may be expected in
areas of substantial alachlor use such as in portions of the
corn belt and that occasional levels much higher than this
may be expected on certain days. However, the significance
of these temporarily higher levels for cancer risk assessment
is unknown. Some of the uncertainties of risks associated with
partial lifetime exposure were discussed in Chapter II.D.I.a.
Use of available averages of samples where contamination
was found, rather than modeling estimates, would result in
similar risk estimates. Table 22 presents the upper 95% bound
on estimated lifetime cancer risk for various levels of alachlor
in drinking water. Risk estimates are presented for both the
10 kg child drinking 1 liter of water per day and the 60 kg
adult drinking two liters of water per day. Although a life-
time of exposure is assumed in each case, the available data
do not allow the determination of which individual (the 10 Kg
child or the 60 kg adult) is a more appropriate model. The
range of potential risks indicated by the two models should
be considered. The risk estimates are conservative and subject
to over estimation of risk and tend to stress the Agency's
concern over early exposure.
Table 22. Assessment of Drinking Water Risks for Alachlor*
"Exposure LevelUpper Limit Estimate of
(ppb) Lifetime Cancer Risk
1
0.
1.
5.
15
5
0
10 Kg
1
1
0
0
Child
-6
-5
10~4
60
10
1
1
0
Kg Adult
-7
— D
0-5
to
to
to
10-
10-
10-
6
5
4
estimation.
55
-------
2. Applicator Risks
Estimated applicator cancer risks in Table 23 are for
the exposure situation considered most relevant to actual
application conditions. That situation assumes that the
worker is wearing protective clothing such as coveralls and
rubber gloves during mixing and loading. Rubber gloves are
generally not worn during application. Protective clothing
in this case reduces exposure to covered body areas by 80%
from the case of a worker who is virtually unprotected. A
50% dermal exposure is assumed for all exposures except for
the microencapsulated product for which a 12% dermal absorption
is assumed (Monsanto, 1981a & 1981b). The risk estimates
presented in Tables 24 and 25 are for the exposure situations
which the Agency considers less likely to be applicable to
actual applicator exposure. They are presented to illustrate
the effect of various degrees of protective clothing on
risk.
The estimates of cancer risk to occupationally exposed
persons do not contain any component of dietary or drinking
water exposure. Therefore, the appropriate estimates of
cancer risk to workers using alachlor would be higher than
these estimates because of the dietary exposure routes.
56
-------
Table 23. Alachlor Worker Upper Limit Risk Estimates
80% Protection
Product
LASSO EC
Micro
Encapsulated
Granular
(LASSO II)
Use Pattern
Ground Tank Fill
Ground
Applicator
Ground Transfer
(Closed System)
5 gal container
Ground Transfer
(Closed System)
55 gal container
Aerial**
Application:
Tank Fill
Aerial**
Application:
Pilot
Aerial**
Application:
Flagger
Mixer
Loader
Applicator
Combined
Mixer
Loader
Applicator
Combined
Days/year
1 d/y
30 d/y
1 d/y
30 d/y
1 d/y
30 d/y
1 d/y
30 d/y
5 d/y
10 d/y
5 d/y
10 d/y
5 d/y
10 d/y
1 d/y
30 d/y
1 d/y
30 d/y
1 d/y
30 d/y
1 d/y
30 d/y
1 d/y
30 d/y
1 d/y
30 d/y
Lifetime Exposure*
mg/kg/day
2 x 10~4 -
5 x HT3 -
2 x KT5 -
5 x ID"4 -
2 x 10~5 -
4 x 10-4 -
1 x 10~4 -
3 x ID"3 -
1 x 10-2 -
2 x 10-2 -
5 x 10-4 -
1 x 10-3 -
2 x 10-2 -
3 x 10-2 -
5 x 10-2 -
2 x ID"3 -
5 x 10~6 -
2 x 10-4 -
5 x HP5 -
2 x 10-3 -
4 x ID"4 -
1 x 10-2 -
1 x HT6 -
3 x ID"5 -
4 x 10-4 -
1 x ID"2 -
4 x 10-4
1 x 10-2
3 x 10-3
1 x 10-3
3 x 10~5
8 x 10-4
2 x 10~4
5 x 10-3
2 x 10-2
3 x 10-2
9 x 10-4
2 x ID"3
3 x 10-2
5 x 10-2
1 x 10~4
4 x 10-3
1 x 10-5
4 x 10-4
1 x 10~4
4 x 10-3
8 x ID"4
2 x ID"2
2 x 10~6
6 x ID'5
8 x 10-4
2 x 10-2
Upper 95% Bound
on Risk
10-5 -
10-4 -
10~6 -
10-5 -
ID"6 -
10-5 -
10~6 -
ID"4 -
10-4 -
10-3 -
10-5 -
10-5 -
10-3 -
10-3 -
10~6 -
ID"4 -
10-7 -
10-5 -
10~5 -
10-4 -
10-5 -
10-4 -
10-8 -
KT6 -
10-5 _
10-4 -
10-4
10-3
10-5
10-4
10-5
ID'4
10-5
10-3
10-3
10-2
10~4
10-4
10-2
10-2
10-5
10-3
10~6
ID'4
10-5
10-3
10-4
10-3
10-7
10-5
10-4
10-3
* *
Range represents estimated exposure from applying alachlor at
2 Ibs/acre to 4 Ibs/acre rates.
.Aerial application is being discontinued.
57
-------
Table 24. Alachlor Worker Upper Limit Risk Estimates
No Protection
Product
LASSO EC
Micro
Encapsulated
Granular
(LASSO II)
Use Pattern
Ground Tank Fill
Ground
Applicator
Ground Transfer
(Closed System)
5 gal container
Ground Transfer
(Closed System)
55 gal container
Aerial**
Application:
Tank Fill
Aerial**
Application:
Pilot
Aerial**
Application:
Flagger
Mixer
Loader
Applicator
Combined
Mixer
Loader
Applicator
Combined
Days/year
1 d/y
30 d/y
1 d/y
30 d/y
1 d/y
30 d/y
1 d/y
30 d/y
5 d/y
10 d/y
5 d/y
10 d/y
5 d/y
10 d/y
1 d/y
30 d/y
1 d/y
30 d/y
1 d/y
30 d/y
1 d/y
30 d/y
1 d/y
30 d/y
1 d/y
30 d/y
Lifetime Exposure*
mg/kg/day
2 x ID"3
5 x ID"2
5 x ID"5
2 x ID"3
1 x 10~3
2 x 10-2
1 x 10-3
1 x 10-2
4 x ID"2
1 x lO-1
2 x 10~3
4 x ID"3
5 x ID"2
1 x 10-1
1 x 10-4
4 x 10-3
5 x 10~6
4 x 10-4
5 x 10-5
2 x 10-3
2 x 10-3
5 x ID"2
3 x 10-6
2 x 10-4
2 x 10-3
1 x ID"4
- 3 x 10-3
- 9 x ID"2
- 1 x 10~4
- 3 x ID"3
- 2 x 10"3
- 6 x 10
- 2 x 10-3
- 2 x 10-
- 7 x 10-2
- 2 x 10°''
- 4 x 10-3
- 7 x 10~3
- 1 x 10"1
- 2 x 10-1
- 2 x 10-4
- 7 x 10-3
- 1 x 10-5
- 4 x 10-4
- 1 x ID"4
- 4 x ID'3
- 4 x 10-3
- 1 x 10'1
- 6 x 10~6
- 2 x 10-4
- 4 x ID'3
- 1 x ID'1
Upper 95% Bound
on Risk
10-4 -
10-3 _
10~6 -
10-4 _
10-5-
10-3 -
10-5 -
10-4 -
10-3 _
10-3 -
10-4 -
10-4 _
10-3 -
10-3 -
1C-6 -
ID"4 -
10-7 _
10-5-
10~6 -
10-4 _
10-4 _
10-3 -
10~7 -
10~6 -
ID"4 _
10-3-
10-3
10-2
10-5
10-3
ID"4
10-2
ID"4
10-3
10-2
10-2
10-3
10-3
10-2
10-2
10-5
10-3
10~6
10-4
10-5
10-3
10-3
10-2
ID"6
10-5
10-3
10-2
Range represents estimated exposures from applying alachlor at from
2 Ibs/acre to 4 Ibs/acre rates.
** Aerial application is being discontinued.
58
-------
Table 25. Alachlor Vforker Upper Limit Risk Estimates
100% Protection
Product
LASSO EC
Micro
Encapsulated
Granular
(LASSO II)
Use Pattern
Ground Tank Fill
Ground
Applicator
Ground Transfer
(Closed System)
5 gal container
Ground Transfer
(Closed System)
55 gal container
Aerial**
Application:
Tank Fill
Aerial**
Application:
Pilot
Aerial**
Application:
Fl agger
Mixer
Loader
Applicator
Combined
Mixer
Loader
Applicator
Combined
Days/year
1 d/y
30 d/y
1 d/y
30 d/y
1 d/y
30 d/y
1 d/y
30 d/y
5 d/y
10 d/y
5 d/y
10 d/y
5 d/y
10 d/y
1 d/y
30 d/y
1 d/y
30 d/y
1 d/y
30 d/y
1 d/y
30 d/y
1 d/y
30 d/y
1 d/y
30 d/y
Lifetime Exposure*
mg/kg/day
4 x 10-5 -
5 x 10-4 _
1 x 10-5 _
3 x 10~4 -
1 x 10~5 -
3 x 10-4 _
3 x 10-5 _
5 x 10-4 _
5 x 10~4 _
1 x 10~3 -
1 x 10-4 _
3 x 10-4 _
5 x 10-3 _
1 x 10-2 -
5 x 10-5 _
2 x 10~3 _
5 x 10-6 _
2 x 10-4 _
5 x 10-5 _
2 x 10-3 _
2 x 10~6 -
1 x 10-4 _
3 x 10-7 -
1 x 10-5 _
5 x ID"6 -
1 x 10-4 _
8 x 10-5
1 x ID"3
2 x 10-5
5 x 10-4
2 x 10-5
6 x 10-4
5 x 10-5
1 x 10-3
9 x ID"4
2 x 10-3
2 x 10-4
5 x ID"4
9 x 10-3
2 x ID"2
1 x 10-4
3 x 10-3
1 x 10-5
4 x ID'4
1 x 10-4
4 x 10-3
4 x 10~6
2 x 10-4
6 x 10-7
2 x 10-3
1 x 10-5
2 x 10-4
Upper 95% Bound
on Risk
10~6 -
10-5 _
10-7 -
10-5 -
10-7 _
10-5 -
10~6 -
ID"5 -
10-5 -
10-5 -
10~6 -
10-5 -
10-4 _
10-4 _
10~6 -
10-4 -
10-7 _
10-5 _
10-6 _
10-4 _
10-7 _
10~6 -
10-8 _
10-7 _
10-7 _
10~6 -
10-5
10-4
10~6
10-4
10~6
10-4
10-5
ID"4
10-4
ID'4
10-5
10-4
10-3
10-3
10-5
10-3
10~6
10-4
10-5
10-3
10~6
10-5
10-7
10~6
ID"6
10-5
fron 2 Ibs/acre to 4 Ibs/acre rates.
** Aerial application is being discontinued.
59
-------
3. Uncertainties in the Risk Assessment
The risk assessment approach contains a number of uncertain-
ties, the sources of which have been discussed above.
The quantitative risk estimates contain a great deal of
uncertainty because they must necessarily extrapolate from
laboratory animals to humans and from the very high exposures
used in the laboratory studies to the generally much lower
and less well characterized human exposures. The Agency's
approach has been to present plausible upper bounds to the
risk as a rough indication of what potential risks might be.
Dietary exposure estimates are a source of uncertainties,
some of which have been discussed in Chapter II.C.I.a. Estimates
of residues in meat, milk, poultry and eggs are hampered by the
lack of adequate residue data. The levels of the parent compound
and the metabolites containing the diethylaniline moiety may be
less than the tolerances set at the sensitivity of the analytical
method (0.02 ppm) and the use of 0.02 ppm as a residue estimate,
therefore, may tend to overestimate the exposure and risk assoc-
iated with the parent compound.
On the other hand, insufficient data are available on the
metabolism of alachlor in domestic animals and the transfer of
alachlor residues from treated feeds to animal tissues and milk.
It may be that there are metabolites of toxicological concern
which are not being measured by the available analytical method
used to determine compliance with the tolerances. The total
residue of concern, therefore, may turn out to be higher than the
currently permitted maximum level. Additional metabolism data
are being required as a basis to maintain alachlor registrations
even during the period of administrative review of this chemical.
In order to avoid suspension of the registration under FIFRA
§3(c)(2)(B) data "call-in" provisions, the registrant must submit
such data in the near future (see Registration Standard for
alachlor).
Similarly, there are indications that the present enforce-
ment method associated with the soybean tolerances does not
measure the entire residue of concern on this crop. The level
of the total residue of concern may, therefore, be higher than
indicated here. Additional data are also being requested on
this issue.
Variation in individual food intake patterns is another
source of uncertainty in estimating health risks from dietary
exposure to alachlor. The dietary burdens in the dietary risk
table (Table 20) were based upon standard food factors used by
the Agency for many years to represent typical diets. Although
these standard food factors are appropriate for estimating average
population risk, some individuals and subgroups within the pop-
ulation will be at greater (or lesser) risk because their
diets contain more (or less) of the food with alachlor residues.
60
-------
Some of the uncertainties of risks associated with partial
lifetime exposures were discussed in Chapter II.D.I.a.
Finally, none of these dietary exposure estimates include
the contribution of contaminated drinking water to total dietary
intake of alachlor. The extent of drinking water contamination
by alachlor is itself an uncertainty and the limitations of the
available monitoring data have been previously discussed.
Uncertainties also exist in the area of applicator exposure
and risk, and the primary uncertainty in this area relates to
dermal absorption. The previously submitted dermal absorption
studies suggest rates of 50% for all formulations other than
the microencapsulated product for which a rate of 12% is suggested.
However, the available studies have serious deficiencies in study
methodology which have led to the requesting of additional
information regarding the dermal absorption of all three formu-
lations .
E. Toxicity of Alternatives to Alachlor
Table 26 summarizes the use patterns for the most likely
alternatives to alachlor. Based on the current and projected
use patterns of these compounds the primary alternative appears
to be metolachlor.
Metolachlor has a fairly complete toxicology data base,
lacking only mutagenicity studies, and a Registration Standard
was issued in 1979. Four studies examining the oncogenic potent-
ial of metolachlor have been submitted to the Agency. Two of
these studies were in the Sprague-Dawley strain of rat and were
found to be positive for the induction of neoplastic nodules in
the liver at the highest tested dose level of 3000 ppm. The
National Academy of Sciences (1980) has concluded that "the
neoplastic nodule is a manifestation of the process of hepato-
carcinogenesis...It is induced by a variety of hepatocarcinogens
but not by noncarcinogenic agents." However, two mouse studies
of metolachlor are considered to be negative with respect to
oncogenic potential. The potential of metolachlor to cause
cancer in laboratory animals, therefore, is substantially less
clear than the weight of evidence on the carcinogenic potential
of alachlor.
Based on the chronic rat study, the oncogenic potency of
metolachlor (as indicated by the Q-^* of 2.1 x 10~^) appears to
be much less than that of alachlor. However, it is noted that
the testing of these two compounds was conducted by different
laboratories and used different strains of rats. The use patterns,
dietary Theoretical Maximum Residue Contributions, applicator
exposure patterns and potential for drinking water contamination
appear to be similar for the two compounds.
61
-------
Table 26. Toxicity Data Base for Alternatives to Alachlor
Pivotal Data
Data Gaps
Basis for Acceptable Daily
Intake Calculation
Metolachlor - 6 month dog feeding, NOEL = lOOppm
- 2-Year supplementary (IBT) onco. in
rat: weak oncogen i.e. liver tumors;
- 2-Year chronic in rat (repeat study):
weak oncogen - liver tumors, NOEL =
30 ppm (testicular atrophy)
- 2-Year onco. in mouse negative at
3000 ppm (Highest Dose Tested (HDT))
Industrial Bio-Test, validated)
- 3-generation rat reproduction = 300 ppm
- Teratology rat NOEL = 360 mgAg (HDT)
- Teratology rabbit NOEL = 360 mg/kg
- Mutagenicity: negative (2 tests)
- Positive skin sensitizer
- 2-Year onco. in mouse: negative at
3000 ppm (HDT)
Vernolate - 2-Year mouse feeding/onco. negative
NOEL > 100 mgAg/day (HDT)
Pendimethalin - Rabbit teratology, NOEL =
60 mg/kg (HDT)
- 2-Year dog feeding, NOEL =
12.5 mg/kg/day (hepatic toxicity)
- Mutagenicity: negative (2 tests)
Metribuzin - Rabbit teratology; NOEL =15 mg/kg/
(HDT)
- Mutagenicity: negative (3 tests)
All the other Pivotal data were not
Core classified:
- 2-Year dog feeding, NOEL = 100 ppm
- 2-Year rat feeding/onco., negative
for oncogenicity; NOEL = 300 ppm
- 2-Year mosue onco. negative at
3200 ppm (HDT)
- 3-Gen. reproduction, NOEL =300 ppm
- Rat teratology, NOEL = 100 mg/kg (HDT)
Additional mutagenicity
All other pivotal data:
chronic, onco., terato
and reproduction
All other pivotal data
Several pivotal studies
were not Core classified
and will be reevaluted in
the Registration Standard.
6-month dog feeding,
NOEL = 100 ppm weak
oncogen: liver tumors,
0*i = 2.1 x 10~3
90-day rat feeding, not
Core classified*: NOEL
640 ppm
90-day rat feeding, not
Core classified: NOEL =
500 ppm
Two-year dog feeding,
not Core classified:
NOEL = 100 ppm
*The core classification system was developed by the Office of Pesticide Programs in 1977 to assess the adequacy
of toxicology studies.
62
-------
Table 26. Toxicity Data Base for Alternatives to Alachlor (Continued)
Pivotal Data
Data Gaps
Basis for Acceptable Daily
Intake Calculation
Oryzalin
Trifluralin
3-Gen. reproduction NOEL =
250 ppm (LDT)
Rat teratology NOEL = 225 ppm
(HOT)
Rabbit teratology NOEL =125
mg/kg (HOT)
Chronic feeding/onco. in mouse
NOEL = 500 ppm, not oncogenic
at 3650 ppm (HOT)
2-Year rat feeding/onco.: NOEL =
300 ppm, potential oncogen: skin
tumors.
Mutagenicity: negative (3 studies)
Rabbit teratology, NOEL = 450
mg/kg (Supplementary Data)
4-Gen. rat reproduction, NOEL
= 200 ppm (LDT) (Supplementary
Data)
All other pivotal data were not
Core classified:
Mouse onco: positive,
hepatocellular
adenoma and carcinoma,
alveolar-bronchiolar adenoma,
and squamous-cell carcinoma in
female mice.
Rat onco: negative at 6,500 ppm
(HOT)
Reproduction - dog, NOEL = 25 mg/kg
2-Year feeding rat, NOEL = 2,000 ppm
3-Year dog, NOEL =10 mg/kg (liver
weight changes)
2-Year dog, NOEL =10 mg/kg (HPT)
One mutagenicity study:
dominant lethal
Pending re-evaluation of
pivotal data
90-day rat feeding not
Core classified
NOEL =750 ppmgen in
Potential oncogen in
rat: skin tumors.
Oj* = 3.375
x 10'
,-2
90-day dog feeding,
not Core classified:
NOEL = 400 ppm
63
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Table 26. Toxicity Data Base for Alternatives to Alachlor (Continued)
Pivotal Data
Basis for Acceptable Daily
Data Gaps Intake Calculation
Propachlor - Rat teratology, NOEL = 200 ppm
(HOT) All the other pivotal data
are not adequate to regulate this
chemical: invalid or unvalidated
IBT studies.
Diphenamide Pivotal data not Core classified:
- 3 Gen. reproduction, NOEL = 10 mgAg
(fetotoxicity)
- 2-Year rat feeding, NOEL = 10 mg/kg
- 2-Year rat feeding, NOEL = 3 mg/kg
Atrazine - Rat teratology, NOEL = 100 mg/kg
- Negative mutagenicity (1 study)
The other pivotal data are not adequate
(Core supplementary) to regulate this
chemical:
- 2-Year dog feeding, NOEL =150 ppm (LOT)
- 3-Gen. rat reproduction, NOEL = 100 ppm
(HOT) using the SOW formulation
Simazine - 3-Gen. reproduction NOEL > 100 ppm
(only one dose tested)
- A questionable 2-year chronic feeding/
onco. study in rat needs to be
repeated, (NOEL > 100 ppm (HOT) using
a 50% a.i. product)
Cyanazine - teratology in Fisher rat: a
potential weak teratogen, (NOEL for
study not yet determined: 10 mg/kg
for micrcophthalmia/anophthalmia,
and pending additional studies, the
NOEL may be lower than 1 mg/kg (LOT)
for liver induced hernia)
- teratology in SD rat: negative at 30 mg/kg
(HOT), (however, MTD not tested).
- teratology in rabbit: negative at 4 mg/kg
(HOT), NOEL = 1 mg/kg/day
- 2-year onco. in mice: negative at 1000 ppm
(HOT)
IBT replacement studies
for all subchronic,
chronic, and teratology
data base.
Pending reevaluation of
pivotal data. Also no
teratology study was
initially submitted.
Extensive data gaps: All
chronic, teratology,
reproduction and additional
mutagenicity.
Extensive data gaps: All
chronic and teratology.
A questionable onco. in
rat needs to be replaced.
All other pivotal data:
chronic in 2 sp., onco.
in rat, 3-gen. repro-
duction and additional
mutagenicity studies
90-day rat feeding,
unvalidated IBT study
with a NOEL = 266 ppm
2-Year dog feeding,
not Core classified:
NOEL = 3 mg/kg
2-Year dog feeding.
Core supplementary:
NOEL =150 ppm
Apparently an Invalid
study (unidentified at
the present time) was
used for ADI calcula-
tion.
2-Year rat feeding,
Core supplementary:
NOEL =12 ppm
64
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.**6 duct ion Measures
On June 19, 1984, Monsanto Chemical Co. submitted to the
Agency risk reduction measures which the company proposed as
conditions for the continued registration of alachlor. The
Agency has examined each proposal. Presented below is the
Agency determination of the impact of each risk reduction
measure.
0 Monsanto proposed to make a transition from the
emulsifiable concentrate (EC) formulation to the microencap-
sulated (ME) formulation within the next five years. In the
ME formulation alachlor is encapsulated in a polymer shell
and suspended in a water formulation. The same amount of
alachlor is applied per acre as with the EC, but Monsanto
contends that the encapsulation process considerably reduces
applicator exposure. The registrant estimates that applicator
exposure to "free alachlor" will be reduced by more than 95%
with the ME compared to the EC formulation. This would
reduce applicator risk very substantially. However, no study
has been received by the Agency which addresses the determination
of "free alachlor" in the aqueous phase in the ME or any
other formulation. The basis for the registrant's conclusion
that potential exposure from the ME is only 2.6% of that for
the EC is unclear. The Agency cannot assume that occupational
exposure will be reduced to such an extent unless data are
submitted to substantiate the claim.
0 Monsanto proposed to eliminate all aerial application of
alachlor products. The Agency supports the elimination of all
aerial application uses of alachlor and that has been accomp-
lished via the Registration Standard.
0 Monsanto proposed elimination of the 6 and 8 Ib/acre
rates on soybeans. This alters one of the higher applicator
exposure situations. The Agency accepted this proposal.
0 Monsanto proposed to clarify and/or add protective
clothing statements to alachlor labels. The Agency is imposing
the addition of protective clothing statements for alachlor
labels in the Registration Standard. The risk estimates in
Table 23 which are predicated on the wearing of such protective
clothing.
0 Monsanto proposed to drop the use on potatoes from the
alachlor labels. Potatoes represent the second highest
contribution to the calculated Theoretical Maximum Residue
Contribution (TMRC). Monsanto stated that withdrawing potatoes
represents a 23.6% decrease in the TMRC which would result in
a corresponding reduction in any dietary risk calculation.
The results of this reduction are illustrated in Table 27.
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0 Monsanto proposed to develop methods and data to support
a 10-fold reduction in meat, milk and egg tolerances. Current
tolerances for these commodities are 0.02 ppm. If the tolerances
for meat, milk and eggs were reduced to 0.002 ppm, a 35%
reduction in the TMRC would result. Added to the withdrawal of
potatoes, the registrant noted that this results in a 59%
reduction in TMRC and a corresponding decrease in dietary risk
calculations. Table 27 also shows the calculations resulting
from the proposed lower tolerances. There is no change in
the order of magnitude of the estimated risk. At the current
time the Agency has no basis to assume that lower tolerances
can be established for meat, milk and eggs. There is no
adequate validated methodology available to measure residues
below 0.02 ppm and that available methodology appears unable to
measure certain metabolites which may represent significant
portions of the residues of interest. Also, the metabolism
of alachlor in animals is not understood. There are no valid
feeding studies available reflecting maximum possible dietary
intake of alachlor and its metabolites by animals. The
analytical methodology and appropriate data are being required
by the Registration Standard.
66
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Table 27. Effect of Monsanto Proposals on
Estimates of Dietary Risk
DeletionDeletion of Potatoes
Current of & Reduction of Milk,
Risk Potatoes Meat, Egg Tolerances
TMRC (tolerance level) 6 x 10~4 4 x 10~4 2 x 10~4
RISK 3 x 10-5 3 x 10~5 i x iQ-5
% Of ORIGINAL RISK 100 76 42
ESTIMATE
Actual residue 4 x 10~4 3 x 10~4 1 x 10~4
level
RISK 3 x 10~5 2 x 10~5 7 x 10~6
% Of ORIGINAL RISK 100 75 29
ESTIMATE
67
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0 Monsanto proposed grazing restrictions on peanuts or,
alternatively, on everything but corn and sorghum. The
restriction on feeding of peanut forage and hay would lower
the average dietary burden of livestock, but the inadequacy
of available metabolism, feeding and residue data does not
allow the conclusion that the resulting residue level would
be lower in meat, milk, poultry and eggs than 0.02 ppm. The
data are being required by the alachlor Registration Standard.
A recently submitted study indicates only 10% of soybean foliar
and bean residues is converted to the 2,6-diethylaniline
moiety which is measurable by available analytical methodology.
The study demonstrates that 50% and 40%, respectively, of the
total soybean foliar and bean 14C residues contain alachlor
metabolites convertible to 2-ethylaniline upon acid hydrolysis
which will be detected by current methodology.
0 Monsanto also suggested that the Agency consider the
actual percentage of the crop that is treated in its estimate
of dietary cancer risk. The Agency notes that the percentage
of total acres treated with alachlor are 31, 28.5 and 38% for
corn, soybeans and peanuts, respectively, based on a 1982
USDA survey. The percentage of acres of potatoes that is
treated is much less (less than 2% of the total potato acreage).
Since the use on potatoes is being cancelled, the Agency
finds that the remaining risk is not substantially reduced by
any attempt to adjust dietary risk for the percentage of
corn, soybeans and peanut acres that are actually treated
with alachlor. If the estimated exposures from directly
consumed treated crops were reduced to reflect percentage of
major crops treated, any such reduction could not be extrapolated
to residues in animals and animal products because of the
substantial gaps in our understanding of animal metabolism.
The reduction in estimated average dietary risk would be
about 10% for the general population assuming a uniform
distribution of treated corn, soybeans and peanuts in individual
diets and the reduction in risk will be even less for certain
geographical areas where treated commodities are consumed at
rates higher than the national average. In light of all the
uncertainties inherent in the estimates of dietary exposure,
the adjustment for percentage of major crop treated would not
substantially improve the reliability of those estimates.
As evidenced by the above discussions, the risk reduction
proposals suggested by Monsanto and adopted by the Agency are
not sufficient to negate the need for a Special Review on
alachlor.
68
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III. Benefits Summary
A. Introduction
Alachlor is an herbicide produced in the U.S. by Monsanto
Chemical Co. It has been estimated that in recent years
approximately 90 to 95 million pounds of alachlor have been
used annually as a pesticide active ingredient. Sites treated
include preemergent application to corn, soybeans, peanuts,
beans, potatoes, cotton, peas, sorghum, sunflowers, and
ornamentals.
The information used to assess the benefits of alachlor
was jointly derived from several sources - USDA, the States,
Monsanto Chemical Company, Ciba-Geigy Corporation, and the EPA.
The general approach of this analysis is to evaluate the economic
impacts of an alachlor cancellation causing users to shift to
alternative weed control agents. The alternatives to
alachlor were chosen on the basis of cost, efficacy, and
availability. Economic impacts on users, as well as for
commodity markets and consumers are based on changes in
production costs, crop yield reductions, and possible grower
shifts to other agricultural enterprises. Impacts on users
are considered on both a per-unit and aggregated basis at
the regional and national level. Grower impacts are then
utilized for projections at the commodity and consumer levels,
where appropriate.
Analyses of the data available indicated the range of lost
benefits of $40 million to $345 annually million depending on the
alternatives adopted. Examination of the data and results
indicate that the most likely first year loss in benefits would
be about $157 million (Table 28). It is expected that impacts
would remain near $157 million for 2 to 3 years following a
cancellation of alachlor use. Economic impacts would then be
expected to decline as existing weed control methods are
adopted or new technologies become available. After 5 to 8
years, farmers and markets should be fully adjusted to the loss
of alachlor. This represents losses due to both the increased
cost of weed control and the decreased value of crop production.
Cost estimates for continued use of alachlor are based on
current costs and do not reflect any increases in the costs of
using alachlor which might result from labeling changes such as
classification for restricted use or requirements for protective
clothing which were instituted with the issuance of the Registration
Standard for alachlor. Those changes could affect the cost of
alachlor use enough to remove the advantage in weed control
costs which existed prior to the Registration Standard.
Monsanto Chemical Company advertising claims a 4 average
69
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bushel gain in corn yields for alachlor over metolachlor. If
these estimates are accurate there would be losses to society
of $330 to $430 million with consumer expenditures increasing
by $670 to $800 million and farmers as a group experiencing
gains of from $340 to $400 million. Although data were not
available to indicate the distribution of the gains among
alachlor users and non-users, indications are that those who
do not use alachlor would experience the gains and users of
alachlor would have a decrease in net returns. The impacts
from the 4 average bushel gain in corn yields would represent
a worst case projection of impacts of a loss of alachlor and
do not take into account use of herbicides other than metolachlor
as alternatives to alachlor on corn.
The magnitude of the impact of a loss of alachlor is highly
dependent on the weed control programs which are used to replace
alachlor. These programs would depend on the weed spectrums on
those acres currently treated with alachlor and the portion of
the acres with each weed spectrum. This information is not
available. Therefore, the analysis of the loss of alachlor was
based on the assumption that alternatives would replace alachlor
at the same relative frequency as they are currently used.
The $10.5 million production loss for peanuts is the only
such figure presented in Table 28. Determinations of production
loss for other crops would be possible only if the entire product
performance data base for alachlor vs. the alternatives were
available; however, the wide range of available alternatives
in most circumstances makes widespread production losses unlikely
There could be localized conditions where the use of alternatives
would result in production losses to individual producers which
could not be estimated with the information available.
If alachlor were unavailable for use on corn and soybeans,
this analysis has assumed that in the first year after
cancellation farmers would shift to the use of alternative
herbicides. Since yield effects are expected only on peanuts
and production costs have been higher with alternative controls,
the earnings of some corn and soybean farmers would diminish.
In the second and succeeding years, some corn and soybean
farmers might respond to this lower income by shifting to the
production of other profitable crops (mostly small grains or
cotton).
It is estimated that about $20 to $25 million of the farm
income loss would be shifted to consumers, an amount which is
negligible in light of the total $21 billion domestic expenditure
for corn and soybeans.
In calculating these impacts, it was assumed that only
currently registered pest control methods would be available
at the time of an alachlor cancellation. The estimated
70
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output loss to peanut growers is due to yield effects in south
eastern states (Alabama, Florida, and Georgia) where weed
control problems can not be alleviated with metolachlor, the
most likely alternative (Schneider, 1984; Torla, 1984). Other
herbicides not currently registered but showing promise for
weed control in peanuts include : ethafluralin, vernolate,
sethoxydim, acetochlor and fluazifop-butyl. It is not known
if any of these chemicals will receive full registration or
will serve as suitable alternatives.
In this preliminary assessment, EPA has not analyzed the
economic impacts of the various potential changes in terms and
conditions of continued registration which are identified as
options in Chapter IV.
B. Field Corn
The loss of alachlor is estimated to increase cost of weed
control of field corn by about $118 million assuming the cost
of continued use of alachlor does not increase due to additional
labeling requirements. The per acre weed control costs are
estimated to range from a decrease of $7.37 per acre to an
increase of $11.59 per acre. Variations in the production
cost impacts are dependent on the particular weed problems and
the cost of alternative controls (Torla, 1984).
There are limitations on the biological data base which
could influence the estimates of the magnitude of the economic
impacts of regulatory actions on alachlor. This analysis assumes
that a shift to alternative weed controls would not result in
any reduction in yields. Although data were not available to
prove no yield losses would occur, available data indicated
this to be a reasonable assumption. For most cases, this is a
reasonable assumption since several alternatives are available
to replace alachlor and a user should be able to identify a
weed-control strategy without alachlor which would give compar-
able control. However, for no-till operations, which represent
3 percent of the affected acres, only metolachlor could replace
alachlor and conditions such as regional weed infestations
could exist for some producers where metolachlor would not be
as effective and yield losses would result.
Certain limitations may affect the usefulness of alachlor
alternatives. Examples of these limitations are soil texture,
fertilizer compatability, need for soil incorporation and ap-
plication technique. In no case do these limitations apply to
every alternative to alachlor. Therefore, it is reasonable to
conclude that at least one effective alternative exists for
any situation (except for the certain no-till operations discus-
sed above). In some situations, the limitations decrease the
cropping options rather than prevent the use of alternative
chemical controls. For example, in the case of crop rotation,
there would be economic hardship in years when a first corn
planting was lost due to cold, wet weather and a second corn
71
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planting without alachlor might be less profitable than planting
to an alternative crop; and when the use of certain alternative
chemicals may prevent the planting of an alternative crop due to
phytotoxicity problems (Szuhay, 1984).
C. Peanuts
The cancellation of alachlor registrations for use on pea-
nuts could result in losses to peanut producers of about $11.4
million annually. This estimate is based on likely decreases
in the value of production of about $10.5 million and increases
in the cost of weed control of about $0.9 million. Although
the lost production is only about one percent of the U.S. pea-
nut crop, it represents losses of about six percent to a portion
of those producers using alachlor which could mean reductions
in net returns of 40 to 60 percent for the producers in Alabama,
Florida and Texas. The peanut crop is under a governmental
allotment program and the USDA has been reducing the quantity
of peanuts allowed to be produced because of surplus production.
Therefore, the impact of any loss is expected to be borne
directly by the producer and not shifted to the consumer (Torla,
1984) .
The available biological data base for peanut production
indicates that yield reductions could be expected for producers
in certain geographical areas. In Oklahoma, copperleaf is a
major weed pest in peanut fields. Metolachlor, the major
alternative to alachlor on peanuts, does not control copperleaf.
Control problems are also expected in Alabama, Florida and
Texas. With the loss of alachlor, one additional cultivation
would be necessary (in addition to metolachlor use) in all
regions. Additional cultivations would require a fungicide
spray at the time of cultivation to prevent white mold disease
(Schneider, 1984). The estimated changed cost in weed control
identified above takes into account the costs of increased
cultivation and increased fungicide use in these areas.
D. Soybeans
The cancellation of alachlor use on soybeans is estimated
to result in increased weed control costs of about $28 million.
The per acre treatment cost impacts of an alachlor cancellation
would range from a reduction of $2.26 to an increase of $9.55.
Variations in the production cost impacts were dependent on the
particular weed problems and the cost of alternative controls
(Torla, 1984).
There were limitations on the biological data base which
could influence the estimated magnitude of the economic impacts
of a cancellation of alachlor. It was assumed that a shift to
alternative weed controls would not result in any reduction in
yields. For most situations, this is a reasonable assumption
72
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since alternatives will control most target weeds (Keitt, 1984).
E. Sweet Corn and Popcorn
It was estimated that a loss of alachlor use on popcorn and
sweet corn would result in increased weed control costs of about
$900,000. Since there is a very close similarity in growing
conditions for field corn, popcorn and sweet corn, the reasons
that losses are not expected for field corn also apply to
these uses.
Sweet corn and popcorn are usually of higher unit value
than field corn. The higher unit value could result in
producers considering minor reductions in yield to be
significant economic losses whereas comparable yield losses
with field corn could be ignored (Torla, 1984).
F. Cotton, Dry Beans, Grain Sorghum, Green Peas, Lima Beans,
Ornamentals, and Sunflowers
It is estimated that a cancellation of alachlor use would
result in a $51,000 increase in the cost of producing cotton;
a $3,000 to $4,000 production cost increase is expected for lima
beans. The cancellation of alachlor use is expected to result
in decreases in weed control costs of producing dry beans,
grain sorghum, green peas, ornamentals, and sunflowers for
those producers currently using alachlor. The magnitude of
these impacts is expected to be small since alachlor is rarely
used on these crops (Torla, 1984).
Alachlor is selected over other available alternatives
for use on these minor crops, probably because of efficacy
and/or crop injury reasons in localized production areas
(Schneider, 1984) .
G. Cabbage - Emergency Action
In a recent (1984) Agency approval of use under FIFRA
Section 18, alachlor was determined to be the most efficacious
weed control method available to cabbage growers in Illinois
for control of Eastern black nightshade, galinoga and yellow
nutsedge (Petrie, 1984).
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Table 28. First Year Economic Impacts of Cancelling Alachlor
Use Site Acres
Planted
(x 1000)
Field corn 83,
Soybeans 70 ,
Peanuts 1 ,
Potatoes 1 ,
Sweet Corn/
Popcorn
Cotton 13,
Dry Beans 2,
Grain sorghum 15
Green peas
(processing)
Lima beans
(green)
Sunflowers 4
371
003
352
251
812
401
047
,936
306
65
,263
Ornamentals n.a.
TOTAL 192
,807
Acres
Treated
(x 1000)
26,400
18,300
111
188-250
203
29-30
242-248
300-600
6-9
6-9
70
nominal
46,521-
46,896
Pounds a.i. Percent
Applied of Crop
(x 1000) Treated
52,300 32
30,900 26
2,398 57
517-687 15-20
406 25
43-45 <1
594 12
737-1,475 2-4
13-20 2-3
13-20 9-14
227 2
nominal n.a.
88,148-
89,072
Percent of Change in
Alachlor Use Cost of
on Crop Treatment
59 118.1
35 28.2
3 0.915
<1 0.100-0.132
<1 0.908
<1 0.051
<1 -.230
1-2 -1.01 to -2.02
<1 -0.02 to -0.03
<1 0.003-0.004
<1 0.326
n.a. n.a.
146.3-147.4
Decrease in User
Value of Impacts
Production
nominal 118.ll
nominal 28. 2 1
10.5 11.4
not determined2 0.100 to
0.132
not determined2 0.908
not determined2 0.051
not determined2 -.230
not determined2 -1.01 to
-2.02
not determined2 -0.02 to
-0/03
not determined2 0.003 to
0.004
not determined2 0.326
not determined2 n.a.
156.8 to
157.9
74
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_!_/ About $20 to S25 million of corn and soybean impact could
be shifted to the consumer.
2/ Decrease in value of production was not determined for
these crops due to the unavailability of comparative product
performance data for alachlor vs. alternatives.
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IV. Additional Grounds for Review
As discussed in detail in Chapter II of this document, data
have shown that alachlor is oncogenic in test animals. The data
and analyses available at this time with respect to dietary
exposure are not sufficient to warrant the issuance of a final
regulatory decision. The Agency specifically solicits further
evidence bearing on these possible adverse effects. All comments
and information received with respect to the potential adverse
effects, including analysis, may serve as a basis for a final
decision on the registration of pesticides containing alachlor.
A. Risk/Benefit Information
The Agency's principal concern is that significant continued
long-term or lifetime exposure to alachlor may pose a risk to
human health. Several long-term feeding studies in laboratory
animals indicate that alachlor causes tumors at a number of
sites in the body and, therefore, human exposure to alachlor
raises public health concerns. There are three sources of
possible human exposure to alachlor.
First, approximately 90 million pounds of alachlor are used
annually to treat about 45 million acres of cropland. As many
as one million persons are involved in handling and applying
alachlor. Most, if not all, are exposed at levels which raise
concerns about human health if exposures were to continue over
their working lifetime.
Second, in an area heavily used for growing the principal
crops on which alachlor is applied, residues in surface water
and ground water used as municipal drinking water supplies are
found to persist at levels which raise concerns about health
risks to persons who might be exposed over long periods.
The third source of possible exposure to alachlor is through
consumption of treated crops containing residues of the chemical.
Information on the extent to which alachlor residues exist in
individual food commodities is very limited. Residues may be
found in treated crops. If all treated commodities and animal
products from animals consuming treated feed were found to
contain alachlor and its important metabolites at or near tol-
erance levels, the resulting exposure to humans over time would
raise serious health concerns.
Estimates of human health risk to alachlor are presented in
Chapter II of this document. Registrants and other interested
persons are invited to examine the basis for the Agency's
decision to initiate the Special Review and may submit data
and information. Registrants and users may also suggest
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methods to reduce risk of use of the pesticide to acceptable
levels.
The regulatory options which will be considered by the
Agency in reaching a final regulatory decision are: (1)
continuation of registration without further changes in the
terms and conditions, (2) continuation of registration with
modification to the terms and conditions of registration, and
(3) cancellation of registration. Some suggested risk
reduction measures short of cancellation on which the Agency
would like to receive comments and information are:
1. Reguiring alachlor to be marketed only in closed
systems.
Handling systems utilizing transfer probes or pumps would
avoid direct handling of the container and would reduce
applicator exposure to the product. Monsanto has committed to
increase the use of bulk and 55 gallon reduced exposure systems
to 55% of the total alachlor sales in 1985 and to 65% by 1987.
The Agency will be examining the feasibility of requiring that
all alachlor be sold in reduced exposure systems.
2. Requiring alachlor to be soil-incorporated.
At the present time only about 25% of the alachlor applied
is incorporated. The Agency is examining the extent to which
runoff and associated surface water contamination can be
eliminated if alachlor is no longer surface-applied. In
conjunction with this, the Agency will also consider the results
of leaching/mobility studies required by the alachlor Registration
Standard. That is, while incorporation of alachlor may reduce
runoff to surface water, it may cause alachlor to leach into
ground water.
3. Restricting alachlor use only to certified applicators.
Restricting the use of alachlor to certified applicators
should help reduce the chance for accidental or careless excess
occupational exposure to alachlor.
4. Limiting application rate of alachlor to 2 Ib/acre.
Monsanto contends that the 4 Ib/acre rate is necessary
for acceptable weed control under conditions of high infestation
of difficult to control weeds, and where soil texture and organic
matter content reduce herbicidal activity. The 4 Ib rate is
used on only 5.2% of the total alachlor treated acres. The
Agency will be considering limiting alachlor application to
2 Ib/acre to further reduce worker exposure. Implications of
this restriction to be considered are a reduction in the
effectiveness of weed control in certain geographical areas
or a reduction in the number of uses for alachlor.
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5. Allowing marketing of only the ME formulation.
Monsanto contends that the ME formulation considerably
reduces applicator exposure to the active ingredient. If
this is true, it may mitigate some of the Agency's concerns.
However, at the present time Monsanto has not submitted the
appropriate data to substantiate the claim.
In order to carry out the benefit analysis of the conse-
quences of limiting or cancelling uses of alachlor, EPA also
solicits comments from registrants, users or other interested
parties in regard to the following aspects, for each crop for
which alachlor is registered. The experience of farmers that
use alachlor, particularly when documented by records, as well
as results of surveys and comparative experiments, is desired.
Of special interest are (1) data from carefully designed and
executed field scale yield comparisons which compare alachlor
with potential alternative herbicides, (2) data which relate
yield differences to one or more specific conditions (of major
importance are soil types, moisture and temperature in relation
to time of planting and application of herbicides, weed pressure,
crop variety, geographic location, and method and timing of
herbicide application), and (3) information on relative crop
tolerance to herbicides and tank mix combinations, especially
in relation to environmental factors, e.g. cold, wet weather
shortly after planting.
Also important is information on:
1. Weed control programs involving alachlor on all
registered sites. Important aspects are:
a. the crop involved (especially those other
than corn, soybeans and peanuts),
b. number of acres treated in the program,
c. regions where the program is used,
d. other chemical, rotational and mechanical
components (e.g. cultivation) of the program,
e. rate, timing, and frequency of application
of herbicides or of mechanical treatments.
2. Alternative weed control practices that would be used
if alachlor uses were limited or cancelled. In addition to the
information supplied under Item 1 above, include:
a. changes in the use of chemical or mechanical
weed controls,
b. other changes in farming practices resulting
from the use of the alternative weed control,
78
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c. advantages and disadvantages resulting from
the change of programs.
3. The impact of limiting or cancelling alachlor use
upon double-cropping, no-till and minimum-till farming, and
other practices designed to conserve soil, energy, and/or
time. Include estimates of the affected acreage and indicate
the region(s) where the impact will occur.
4. The current availability of alternative chemicals or
mechanical equipment, and any expected changes in their prices
if alachlor were to be limited or cancelled.
5. The impacts on commodity export markets if alachlor
use were limited or cancelled.
6. The impact on the cost of agricultural subsidy programs
administered by USDA, if alachlor use were limited or cancelled.
B. Rebuttal Submission Procedures
The registrant and other interested parties will have 45
days from the date this document is received or until 45 days
after the date of publication of the notice in the FEDERAL
REGISTER (whichever is later) to submit evidence in rebuttal
to the Agency's presumption.
C. Duty to Submit Information on Adverse Effects
Registrants are required by Section 6(a)(2) of FIFRA to
submit any additionl information regarding unreasonable adverse
effects on man or the environment which comes to their attention
at any time. The registrant of alachlor products must
immediately submit any published or unpublished information,
studies, reports, analyses, or reanalyses regarding any adverse
effects associated with alachlor in animal species or humans,
and claimed or verified accidents to humans, domestic animals
or wildlife which have not been previously submitted to EPA.
These data should be submitted with a cover letter specifically
identifying the information as being submitted under Section
6(a)(2) of FIFRA. In light of this Special Review and the
requirements of FIFRA 6(a)(2), the registrant should notify
EPA of any studies on alachlor currently in progress, their
purpose, the protocol, the approximate completion date, a
summary of all results observed to date, the name and address
of the laboratory performing the studies, and a statement as
to whether these studies are being conducted in accordance
with the Good Laboratory Practices specified in 48 FR 53946.
79
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D. Public Comment Opportunity
During the time allowed for submission of rebuttal evidence,
specific comments are solicited on the presumptions and analyses
set forth in this Position Document, the FEDERAL REGISTER
notice and in the Guidance Document. In particular, any
documented episodes of adverse effects on humans or domestic
animals should be submitted to the Agency as soon as possible.
Any information as to any laboratory studies in progress or
completed should be submitted to the Agency as soon as possible
with a statement as to whether those studies are in compliance
with the Good Laboratory Practices specified in 48 FR 53946.
Specifically, information on any adverse toxicological effects
of alachlor, its impurities, metabolites and degradation
products is solicited. Similarly, submission of any studies
or comments on the benefits from the use of alachlor is
requested. All comments and information and analyses which
come to the attention of EPA, may serve as a basis for
final determination of regulatory action following the Special
Review.
Information submitted in any comment concerning this
document may be claimed confidential by marking any part or
all of that information as "Confidential Business Information"
(CBI). Information so marked will not be disclosed except in
accordance with procedures set forth in 40 CFR Part 2. A copy
of the comment containing material claimed to be CBI must be
submitted with the CBI portions deleted for inclusion in the
public record. Information not marked confidential may be
disclosed publicly by EPA without prior notice to the
submitter.
During the comment period, interested members of the public
or registrants may request a meeting to discuss the risk issues
and methods of reducing risks. Prior to such meeting, the
Agency will place an agenda and list of meeting participants
in the public docket. Any member of the public interested in
obtaining a copy of the agenda prior to the meeting with the
Agency to discuss issues in connection with this Special Review
should notify the contact person listed in the FEDERAL REGISTER
notice. Any records pertaining to such meetings, including
minutes, agendas and comments received will be filed in Room
236, CM #2, 1921 Jefferson Davis Highway, Arlington, VA. 22202.
80
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REFERENCES
Ahmed, F.E., A.S. Tegeris, P.C. Underwood, et al (1981) Alachlor:
Six-Month Study in the Dog: Testing Facility's Report No. 7952;
Sponsor's Report No. PR-80-015. (Unpublished study including
submitter summary, received Dec. 1, 1981 under EPA Reg. No.
524-316; prepared by Pharmacopathics Research Labs., Inc.,
submitted by Monsanto Co., Washington, D.C., CDL: 246229-A
and 246293.
Atkins, E.L., E.A. Greywood and R.L. Macdonald (1973) Toxicity
of Pesticides and Other Agricultural Chemicals to Honey Bees:
Laboratory Studies. Rev. by Univ. of California, Riverside,
CA., Dept. of Entomology, Agricultural Extension Service.
(Also in unpublished submission received April 2, 1980 under
EPA Reg. No. 464-556, submitted by Dow Chemical U.S.A.,
Midland, MI, CDL: 242149-z).
Baker, B. David, et al (1981) The concentrations and transport of
pesticides in Northwestern Ohio Rivers. Water Quality Laboratory,
Heidelberg College, Tiffin, Ohio.
Baker, B. David. (1982) Pesticide Monitoring Notes 1982. Water
Quality Laboratory, Heidelberg College, Tiffin, Ohio, Dec. 10,
1982.
Baker, B. David. (1983a) Studies of sediment, nutrient and pesticide
loading in selected Lake Erie and Lake Ontario tributaries.
"Part IV Pesticide concentrations and loading in. selected Lake
Erie tributaries, 1982," July 1, 1983. Water Quality Laboratory,
Heidelberg College, Tiffin, Ohio.
Baker, B. David. (19835) Herbicide contamination in municipal water
supplies of Northwestern Ohio. Draft final report by Heidelberg
College, Tiffin, Ohio, under assistance agreement #R00572701 from
U.S.EPA, Oct. 2, 1983.
Baker, B. David. (1984a) A table summarizing our rainwater analyses
for herbicides in a letter to John McManus of Am. Electric Power
Service Corp. from David Baker, Aug. 16, 1984. Heidelberg College;
Tiffin, Ohio.
Baker, B. David. (1984b) Preliminary printout of 1984 data for
pesticide measurements. Personal communication to P.R. Datta,
Sept. 10, 1984. Heidelberg College, Tiffin, Ohio.
Binder, M. Daniel. (1984) Annual Report on water quality treatment
and monitoring, 1981, 1982, 1983 for City of Columbus, Ohio.
Personal communication to P.R. Datta, Sept. 12, 1984.
Carsel, R.F., L.A. Mulkey, M.N. Lorber, and L.B. Baskin. (1984)
In press. The Pesticide Root Zone Model (PRZM): A Procedure
for Evaluating Pesticide Leaching Threats to Ground Water.
U.S. Environmental Protection Agency.
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Ciba-Geigy Corp. (1979) Two-year Chronic/Oncogenicity Oral Toxicity
Study in Albino Rats. Study No. 622-07926. Unpublished study
dated Feb. 9, 1979, performed by IBT, Decatur, 111., submitted
by Ciba-Geigy Corp. CDL: 244166.
Cohen, S.Z., S.M. Creeger, R.F. Carsel and C.G. Enfield (1984)
Potential for Pesticide Contamination of Ground Water Resulting
From Agricultural Uses in Treatment and Disposal of Pesticides.
American Chemical Society Symposium Series #259.
Coleman, D.L. and W.R. Gaffey (1980) A Study of Individuals Exposed
to Alachlor: Ocular Examinations for Uveitis. Unpublished
study received July 30, 1980 under EPA Reg. No. 524-285;
submitted by Monsanto Chemical Co., Washington, D.C.;
CDL: 242943-A.
Daly, I.W., G.K. Hagan,R. Plutnick, et al (1981a) An Eighteen-
Month Chronic Feeding Study of Alachlor in Mice: Project No.
77-1064. Final report. Unpublished study received July 1,
1981 under EPA Reg. No. 524-285, prepared by Bio/dynamics,
Inc., submitted by Monsanto Co., Washington, D.C., CDL:
070168-A, 070169.
Daly, I.W., J.B. McCandless, H. Jonassen, et al (1981b) A Chronic
Feeding Study of Alachlor in Rats, Project No. 77-2065. Final
Report. Unpublished study received Jan. 5, 1982 under EPA
Reg. No. 524-285, prepared by Bio/dynamics, Inc., submitted
by Monsanto Co., Washington, D.C., CDL: 070586-A, 070587,
8,98, 90.
Danhaus, R.G., J.L. Stragy and S. Dubelman (1980) Residues of Alachlor
and Atrazine in Field Treated Corn Following Preemergent and
Lay-by Applications of Lasso" or Lasso1" and Atrazine Tank Mixes;
Report No. MSL-1105. Unpublished study received April 24, 1980
under EPA Reg. No. 524-285; prepared in cooperation with ABC
Labs, Inc., submitted by Monsanto Co., Washington, D.C.,
CDL: 099396.
Dean, J.D., P.P. Jowise, and A.S. Donigian, Jr. (1984) Leaching
Evaluation of Agricultural Chemicals (LEACH) Handbook (EPA-
600/3-84-068) . U.S. Environmental Protection Agency. U.S.
EPA contract #68-03-3116.
Dodd, Nancy (1984a) Memo to Robert J. Taylor and Toxicology
Branch dated June 29, 1984. Feeding of radiolabeled alachlor
metabolites to laying hens. Accession number 252792. Submitted
in connection with EPA Reg. No. 524-316.
Dodd, Nancy (1984b) Memo to Robert J. Taylor and Toxicology
Branch dated July 3, 1984. Feeding of radiolabeled alachlor
metabolites to lactating goats, Accession number 252793.
Submitted in connection with EPA Reg. No. 524-316.
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Environmental Protection Agency (1977) "Drinking Water and
Health" , a report from National Research Council and the
U.S. EPA.
Environmental Protection Agency (1982) STORET Users Handbook.
The Right Answers for STORET Users. Third Edition. February,
1982.
Environmental Protection Agency (1984) Guidelines for Risk
Assessment of Suspected Carcinogens, EPA, Office of Research
and Development, October, 1984 draft.
Farrow, Michael G. (1984) Ijn Vivo Bone Marrow Chromosome Study
in Rats with Alachlor. Unpublished study dated March 1, 1984,
submitted under EPA Reg. Nos. 524-285, 296, 314 and 316, prepared
by Hazelton Labs., Inc., Vienna, Va . 22180, submitted by Monsanto
Chemical Co., Washington, D.C., CDL: 253308.
Fink, R., et al (1979) Final Report: Acute Oral LD^Q - Bobwhite
Quail: Project No. 139-179. Unpublished study recieved
June 1, 1981 under EPA Reg. No. 524-285, prepared by Wildlife
International Ltd., submitted by Monsanto Co., Washington,
D.C., CDL: 245260-A.
Forbis, A.D. , and W.A. McAllister (1978) Acute Toxicity of Technical
Alachlor to Rainbow Trout ( S a Into gairdineri) . Unpublished
study received August 16, 1978 under EPA Reg. No. 524-385,
prepared by Analytical Biochemistry Laboratories, Inc. sub-
mitted by Monsanto Co.
Frank, R. (1984) Communication prepared by Richard Frank,
Ontario Ministry of Agriculture and Food, University of
Guelph, July 27, 1984.
Hallberg, G.R., B.E. Hoyer, E.A. Bettis, and R.D. Libra. (1983)
Hydrogeology , Water Quality, and Land Management in the Big
Spring Basin, Clayton County, Iowa. A report by the Iowa
Geological Survey on contract number 82-5500-02 from the
Iowa Department of Environmental Quality.
Hawf, L., D. McCall and L. Gingerich (1983) Teleconference with
B.A. Schneider, EPA, OPP, BUD, SSB with Monsanto Agricultural
Products, Inc., March 15, 1983.
IARC (1980) IARC Monographs on the Evaluation of Carcinogenic
Risks of Chemicals to Humans, "Some Pharmaceutical Drugs."
Volume 24. international Agency for Research in Cancer,
Lyon, France. September, 1980.
Johanson, R.C., J.C. Imhoff and H.H. Davis, Jr. (1980) Users
Manual for Hydrological Simulation Program - Fortran (HbPF).
Grant No. R804971-01 for U.S. Environmental Protection Agency.
EPA-600/9-80-015.
Johnson, H.P. and J.L. Baker (1982) Field-to-stream transport
of agricultural chemicals and sediment in an Iowa Watershed:
Part I- Data base for model testing (1976-1978).
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Johnson, H.P. and J.L. Baker (1984) Field-to-stream transport
of agricultural chemicals and sediment in an Iowa Watershed:
Part II: Data base for model testing (1979-1980).
Keitt, G.W., Jr. (1984) Biological Data Base for Exposure
Analysis and Preliminary Benefits Analysis of Alachlor on
Soybeans and Ornamentals. Science Support Branch, BUD/OPP/
OPTS/EPA.
Konishi, Yoichi, A. Kawabata, A. Denda, T. Ikeda, H. Katada,
H. Maruyama and R. Higashiguchi (1980) Forestomach Tumors
Induced by Orally Administered Epichlorohydrin in Male
Wistar Rats. Gann, 71, 922-2. December, 1980.
Kovacs, Martin F., Jr. (1984) Memo to Robert J. Taylor and
Toxicology Branch dated April 23, 1984. PP#OF2348 Alachlor
(Lasso") in or on corn forage and fodder and PPI3F2832
Alachlor on soybean hay. Comments on additional corn and
soybean metabolism studies dated September 16, 1983
(Accession number 251375).
Laskin, Sidney, A.R. Sellakumer, M. Kuschner, N. Nelson, S.
LaMendula, G.M. Rusch, G.V. Katz, N.C. Dulak and R.D.
Albert (1980) Inhalation Carcinogenicity of Epichloro-
hydrin in Noninbred Sprague-Dawley Rats. Journal of the
National Cancer Institute 65 (4): 751-7. October 1980.
Lauer, R., D.D. Arras, J.L. Stranz, et al (1979) Residues of
Alachlor and Atrazine in Field Tested Sorghum Following
Pre- or Postemergent Applications with Lasso™ or a Lasso*
and Atrazine Tank Mix: Report No. MSL-1033. Unpublished
study received March 25, 1980 under EPA Reg. No. 524-285,
prepared in cooperation with ABC Labs., Inc., submitted by
Monsanto Chemical Co., Washington, D.C.; CDL: 099326.
Lauer, R. and D.D. Arras (1981) Aerial and Ground Applicator
Exposure Studies with Lasso" Herbicide Under Actual Field
Conditions. Report No.: MSL-1889. Submitted by Monsanto
Co. CDL: 070591.
Lavy, T.L. (1974) Mobility and deactivation of herbicides in
soil-water systems: Project A-024-NEB. Available from NTIS,
Springfield, VA: PB-238-632; unpublished study received
July 19, 1978 under EPA Reg. No. 201-403; prepared by Univ.
of Nebraska, Water Resources Research Institute, submitted
by Shell Chemical Co., Washington, D.C., CDL: 234472-P.
Libra, R.D., G.R. Hallberg, G.G. Ressmeyer, and B.E. Hoyer.
(1984) I. Groundwater Quality and Hydrogeology of Devonian-
Carbonate Aquifers in Floyd and Mitchell Counties, Iowa.
A report by the Iowa Geological Survey on grant number
G0072737-01 from U.S. EPA.
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Maryland Department of Health and Mental Hygiene (1983)
Results of a Maryland Ground Water Herbicide Survey. A
report on a survey by the Office of Environmental Programs,
Maryland DHMH, Fall 1983.
Miltner, D. (1984) Personal communication to P.R. Data from
D. Miltner, EPA Drinking Water Laboratory, Cincinnati,
Ohio, Sept. 14, 1984.
Mirsalis, J.C. (1984) An Evaluation of the Potential of Alachlor
to Induce Unscheduled DNA Synthesis in the Ir\ Vivo-ln vitro
Hepatocyte DNA Repair Assay. Unpublished study dat^d March
5, 1984, submitted under EPA Reg. Nos. 524-285, 296, 314 and
316, prepared by SRI International, Menlo Park, CA 84025,
submitted by Monsanto Chemical Co., Washington, D.C.,
CDL: 253308.
Monsanto Co. (1967) Metabolism Section - soybeans and corn,
Section D-II of PP # 7F0622. Lasso1". Unpublished study
received under EPA Reg. No. 524-?. CDL: 115143.
Monsanto Co. (1969) Metabolism Section - Peanuts and cotton.
Section D-II of PP # 9F0776. Lasso1". Unpublished study
received under EPA Reg. No. 524-?. CDL: 115827.
Monsanto Co. (1973) Section A of Pesticide Petition No. 3F1406,
submitted by Monsanto Co. RGB Accession No. 118284.
Monsanto Co. (1978a) Acute Oral-Rat, Acute Dermal-Rabbit.
Submitted by Bio-Dynamics, Inc., PD-77-433 on June 28, 1978
Unpublished study received 1978; CDL: 241273.
Monsanto Co. (1978b) Primary Eye and Primary Dermal irritation-
Rabbit. Submitted by Bio-Dynamics, Inc., PD-77-433 on March
22, 1978. Unpublished study received 1978; CDL: 241273.
Monsanto Co. (1979a) Environmental Chemistry of Alachlor.
Unpublished study received Oct. 17, 1979 under EPA Reg. No.
524-285, 296 and 314, prepared by Monsanto Agricultural
Products Co., submitted by Monsanto Co., Washington, D.C.;
CDL: 241135 & 241136.
Monsanto Co. (1979b) Section A of Pesticide Petition No. 9F2144,
submitted by Monsanto Co. RGB Accession No. 225417.
Monsanto Co. (1981a) Elimination of 14C-alachlor in Monkeys.
Study No. MA-81-261, prepared by the Univ. of California
School of Medicine. Submitted by Monsanto Co., Washington,
D.C., on November 28, 1981. CDL: 070592, 247937.
Monsanto Co. (1981b) rn vitro dermal penetration of 14C-alachlor
in human skin. Study No. UW-81-262, prepared by the Univ.
of Washington School of Medicine, Washington. Submitted by
Monsanto Co., Washington, D.C. on November 20, 1981. CDL:
070592.
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Monsanto Co. (1981c) Acute Inhalation LD5Q-Rat. Submitted by
Bio/Dynamics, Inc., PD-81-183 on Dec. 3, 1981. Unpublished
study received 1981; CDL: 248053.
Monsanto Co. (1982) Environmental Fate of Microencapsulated
Alachlor: Vol I & II. Unpublished study received May 26, 1982
under EPA Reg. No. 524-344, prepared by Monsanto Agricultural
Products Co., submitted by Monsanto Co., Washington, D.C.,
CDL: 070841.
Monsanto Co. (1983a) Rat Metabolism Study. MSL-3198, R.D. 493.
Part I and II. Unpublished study received Oct. 1983 under
EPA Reg. No. 524-316; prepared by Monsanto Agricultural
Products Co., submitted by Monsanto Co., Washington, D.C.;
CDL: 251543 and 251544.
Monsanto Co. (19835) Additional Corn and Soybean Metabolism Studies
to Support the Registration of Lasso™, EC, II and ME. RD No.
489, Special Report MSL-3132. Unpublished study received Sept.
16, 1983 under EPA Reg. Nos. 524-285, 296, 314 and 344;
prepared by Monsanto Agricultural Products Co., submitted by
Monsanto Co., Washington, D.C.; CDL: 251375.
Monsanto Co. (1984a) Dermal Sensitization-Guinea Pig. Submitted
on March 24, 1984. Unpublished study received 1984; CDL:
252772.
Monsanto Co. (1984b) Metabolism of Synthetic 14C-Labeled Plant
Metabolites of Alachlor in Laying Hens, Part I: Distribution
of l^C-Metabolites in Eggs, Tissues and Excretia. RD No. 532.
Unpublished study received in 1984 under EPA Reg. No. 524-314;
CDL: 252792.
Monsanto Co. (1984c) Metabolism of Synthetic 14C-Labeled Plant
Metabolites of Alachlor in Lactating Goats, Part I:
Distribution of 14C Metabolites in Milk, Tissues and Excretia.
RD No. 531. Unpublished study received in 1984 under EPA Reg.
No. 524-314; CDL: 252793.
Mulkey, L.A. and A.S. Donigan (1984) Modeling Alachlor Behavior
in Three Agricultural River Basins. U.S. Environmental
Protection Agency.
NAP (1983) Risk Assessment in the Government: Managing the
Process. National Academy Press, Washington, D.C.
National Academy of Sciences (1980) "Histologic Typing of Liver
Tumors of the Rat." Journal of the National Cancer Institute,
Vol. 64, No. 1, 1980, p.185.
National Research Council (1977) Drinking Water and Health, Report
from National Research Council and U.S. EPA.
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OSTP (1984) Chemical Carcinogens, Notice of Review of Science
and its Associated Principles. Office of Science and
Technology Policy. Federal Register Vol. 9, Tues. May 22, 1984.
pp. 21594-21661.
Petrie, Richard C. and B.A. Schneider (1984) Preliminary
Biological Analysis of Alachlor (090501) Use on Potatoes,
Sunflowers and Grain Sorghum. June, 1984. OPP/BUD/SSB.
Rodwell, D.E., and E.J. Tacher (1980) Teratology Study in Rats:
IRDC No. 401-058; IR-79-020. Unpublished study including
submitter summary, received Oct. 16, 1980 under EPA Reg.
No. 524-385; prepared by International Research and
Development Corp., submitted by Monsanto Co., Washington,
D.C.; CDL: 243506-A.
Schardein, James L. (1984) Teratology Study in Rabbits with Alachlor
(IR-83-045). Unpublished study received in 1984 under EPA
Reg. No. 524-316, prepared by International Research and
Development Corp., submitted by Monsanto Agricultural Products
Co., St. Louis, MO; CDL: 252570.
Schmitt, R.D. (1977) Food Factors. Memorandum: to O.E.
Paynter. September 4, 1977. Environmental Protection
Agency.
Schneider, B.A. and R.C. Petrie (1984) Biological Data Base
(Track B) for Preliminary Benefits Analysis of Alachlor
(090501) Use on Peanuts, Dry Beans (All Types) Including
Lima Beans (Green), Red Kidney Beans and Mung Beans,
Green Peas, Cotton. May, 1984. EPA/OPP/BUD/SSB.
Schroeder, R.D., G.K. Hogan, M.E. Smock, et al (1981) A Three-
Generation Reproduction Study in Rats with Alachlor: Project
No. 77-2066. Final Rept. Unpublished study received July
10, 1981 under EPA Reg. No. 524-285; prepared by Bio/
Dynamics, Inc., submitted by Monsanto Co., Washington, D.C.;
CDL: 070177-A.
Shirasu, et al (1980) Microbial Mutagenicity Study, received
Feb. 1980 under EPA Reg. No. 524-316. Prepared by Institute
of Environmental Toxicology; Kodaira, Japan; submitted by
Monsanto Co., Washington, D.C.; CDL: 248053.
Spalding, R.F., G.A. Junk, and J.J. Richard (1980) Pesticides
in Ground Water Beneath Farmland in Nebraska, August, 1978.
Pesticide Monitoring Journal 14(2): 70-73.
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Stout, L.D., et al (I983a) A Chronic Study of Alachlor Admin-
istered in Feed to Long-Evans Rats. EHL #800218, Project
#ML-80-186, Report MSL-3282/3284. Vol. I & II. Unpublished
study received Feb. 28, 1984 under EPA Reg. No. 524-316,
prepared by Monsanto Environmental Health Laboratory(EHL)
submitted by Monsanto Co., Washington, D.C., CDL: 252496-7.
Stout, L.D., et al (1983b) A Chronic Study of Alachlor
Administered in Feed to Long-Evans Rats. EHL #800218,
Project #ML-80-186, Report MSL-3282/3284. Vol. Ill of III.
Unpublished study received Feb. 28, 1984 under EPA Reg. No.
524-316, prepared by Monsanto Environmental Health
Laboratory (EHL), submitted by Monsanto Co., Washington,
D.C., CDL: 252498.
Sutherland, M.L., T.G. Curtis, W.A. Darlington, and J.T. Marvel
(1972) Final report on Lasso and the environment: Part 4:
Photolysis of Lasso on soil and in water: Agric. Research
Report No. 262. Unpublished study received June 29, 1978
under PP # 3F1372; submitted by Monsanto Co., Washington,
D.C., CDL: 093660-L.
Szuhay, D.W. and G.W. Keitt, Jr. (1984) Biological Data Base
for Exposure Analysis and Preliminary Benefits Analysis of
Alachlor on Corn. Science Support Branch, BUD/OPP/OPTS/EPA.
Thompson, C.M., A.D. Forbis, and W.A. McAllister (1978) Acute
Toxicity of Technical Alachlor (AB-78-166) to Bluegill
Sunfish (Lepomis macrochirus). Unpublished study received
August 16, 1978 under EPA Reg. No. 524-283; prepared by
Analytical Biochemistry Laboratories, Inc., submitted by
Monsanto Co., Washington, D.C., CDL: 234628-C.
Torla, R. (1984) Preliminary Benefit Analysis of Alachlor.
Economic Analysis Branch, Benefits and Use Division, Office
of Pesticide Programs, Preliminary Draft, May 1984.
U.S. Environmental Protection Agency (1984) Federal Reporting
Data System. Facilities and Population Served by Drinking
Water Supply Source; Community Active Systems, Not
Including Indian Lands, FY 1983 (FRDS07, April 21, 1984).
Wehtje, G. et al (1981) Atrazine contamination of ground
water in the Platte Valley of Nebraska from nonpoint
sources. The Science of the Total Environment. 21,
47-51, 1981.
Weidner, C.W. (1974) Degradation in ground water and mobility
of herbicides. Master's thesis, Univ. of Nebraska, Dept.
of Agronomy. Unpublished study received July 19, 1978
under EPA Reg. No. 201-403, submitted by Shell Chemical
Co., Washington, D.C., CDL: 234472-O.
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Wilson, G.R., et al (1981) Residues of Alachlor in Sorghum
Forage, Stover and Grain. Report No. MSL-1577. Unpublished
study received May 27, 1981 under EPA Reg. No. 524-285;
prepared by ABC Labs., Inc., submitted by Monsanto Chemical
Co., Washington, D.C.; CDL: 245225.
Yu, C.C., G.M. Booth and D.J. Hansen (1971) Fate of alachlor
and propachlor in a model ecosystem. Unpublished study
received June 29, 1973 under PP # 3F1372; prepared in
cooperation with Illinois Natural History Survey and others,
submitted by Monsanto Co., Washington, D.C., CDL: 093660-Q.
Zager, Edward and Michelle L. Loftus (1984) Memo to Diane
lerley dated August 22, 1984. Residue Chemistry Branch
response to the comments of the Assistant Administrator's
staff on the alachlor Position Document.
U.S . GOVERNMENT PRINTING OFFICEi 1985-461•22 I /24033
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